bluuebunny/crossref_metadata_2025_split huggingface dataset:
Language uncovers visuospatial dysfunction in posterior cortical atrophy: a natural language processing approach
Authors: Rezaii Neguine , Hochberg Daisy , Quimby Megan , Wong Bonnie , McGinnis Scott , Dickerson Bradford C. , Putcha Deepti 
Published: February 2024

IntroductionPosterior Cortical Atrophy (PCA) is a syndrome characterized by a progressive decline in higher-order visuospatial processing, leading to symptoms such as space perception deficit, simultanagnosia, and object perception impairment. While PCA is primarily known for its impact on visuospatial abilities, recent studies have documented language abnormalities in PCA patients. This study aims to delineate the nature and origin of language impairments in PCA, hypothesizing that language deficits reflect the visuospatial processing impairments of the disease.MethodsWe compared the language samples of 25 patients with PCA with age-matched cognitively normal (CN) individuals across two distinct tasks: a visually-dependent picture description and a visually-independent job description task. We extracted word frequency, word utterance latency, and spatial relational words for this comparison. We then conducted an in-depth analysis of the language used in the picture description task to identify specific linguistic indicators that reflect the visuospatial processing deficits of PCA.ResultsPatients with PCA showed significant language deficits in the visually-dependent task, characterized by higher word frequency, prolonged utterance latency, and fewer spatial relational words, but not in the visually-independent task. An in-depth analysis of the picture description task further showed that PCA patients struggled to identify certain visual elements as well as the overall theme of the picture. A predictive model based on these language features distinguished PCA patients from CN individuals with high classification accuracy.DiscussionThe findings indicate that language is a sensitive behavioral construct to detect visuospatial processing abnormalities of PCA. These insights offer theoretical and clinical avenues for understanding and managing PCA, underscoring language as a crucial marker for the visuospatial deficits of this atypical variant of Alzheimer’s disease.
Diverse temporal and spatial mechanisms work, partially through Stanniocalcin-1, V-ATPase and senescence, to activate the extracellular ATP-mediated drug resistance in human cancer cells
Authors: Zhang Haiyun , Song Jingwen , Ward Ryan , Han Yong , Hunt Arabella , Shriwas Pratik , Steed Alexander , Edwards Cory , Cao Yanyang , Co Milo , Chen Xiaozhuo 
Published: February 2024

IntroductionResistance to drug therapies is associated with a large majority of cancer-related deaths. ATP-binding cassette (ABC) transporter-mediated drug efflux, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), glutathione (GSH), senescence, and vacuole-type ATPase (V-ATPase) all contribute to the resistance. We recently showed that extracellular ATP (eATP) induces and regulates EMT, CSC formation, and ABC transporters in human cancer cells and tumors. eATP also consistently upregulates Stanniocalcin-1 (STC1), a gene that significantly contributes to EMT, CSC formation, and tumor growth. We also found that eATP enhances drug resistance in cancer cells through eATP internalization mediated by macropinocytosis, leading to an elevation of intracellular ATP (iATP) levels, induction of EMT, and CSC formation. However, these factors have never been systematically investigated in the context of eATP-induced drug resistance. MethodsIn this study, we hypothesized that eATP increases drug resistance via inducing ABC efflux, EMT, CSCs, STC1, and their accompanied processes such as GSH reducing activity, senescence, and V-ATPase. RNA sequencing, metabolomics, gene knockdown and knockout, and functional assays were performed to investigate these pathways and processes. Results and discussionOur study results showed that, in multiple human cancer lines, eATP induced genes involved in drug resistance, elevated ABC transporters’ efflux activity of anticancer drugs; generated transcriptomic and metabolic profiles representing a drug resistant state; upregulated activities of GSH, senescence, and V-ATPase to promote drug resistance. Collectively, these newly found players shed light on the mechanisms of eATP-induced as well as STC1- and V-ATPase-mediated drug resistance and offer potential novel targets for combating drug resistance in cancers.
Clinicopathological characteristics and outcomes of colorectal mucinous adenocarcinoma: a retrospective analysis from China
Authors: Huang An , Yang Yong , Sun Zhuang , Hong Haopeng , Chen Jiajia , Gao Zhaoya , Gu Jin 
Published: February 2024

BackgroundMucinous adenocarcinoma (MAC) is a unique subtype of colorectal cancer and its prognostic value remains controversial. This study aimed to compare the clinicopathological characteristics and prognostic differences between patients with MAC and non-mucinous adenocarcinoma (NMAC).Methods674 patients with NMAC, 110 patients with adenocarcinoma with mucinous component (ACWM) and 77 patients with MAC between 2016-2019 were enrolled in the study. Univariate and multivariate Cox regression were performed to analyze the factors associated with prognosis. Predictive nomograms of overall survival (OS) and cancer-specific survival (CSS) for patients with colorectal adenocarcinoma were constructed. Confounding factors were eliminated by propensity score matching (PSM).ResultsCompared with patients with NMAC, patients with MAC were more likely to have a tumor located at the proximal colon, present with a larger tumor diameter, more advanced T stage, higher frequency of metastasis, deficiency of mismatch repair, and elevated preoperative carcinoembryonic antigen. Patients with MAC were related to worse OS (HR=2.53, 95%CI 1.73-3.68, p&lt;0.01) and CSS (HR=3.09, 95%CI 2.10-4.57, p&lt;0.01), which persisted after PSM. Subgroup analysis demonstrated that patients with left-sided or stage III/IV MAC exhibited a comparatively worse OS and CSS than those with NMAC. Furthermore, in patients with stage II with a high-risk factor and stage III MAC, adjuvant chemotherapy was associated with an improved OS, CSS, and RFS.ConclusionCompared with the NMAC phenotype, the MAC phenotype was an independent risk factor for poor prognosis in colorectal adenocarcinoma with worse OS and CSS, particularly patients with left-sided colorectal cancer and stage III/IV. However, patients with MAC can still benefit from adjuvant chemotherapy.
Achieving complete remission in metastatic hepatocellular carcinoma with sintilimab plus sorafenib therapy followed by hepatic resection: a case report
Authors: Cui Kai , Li Zhongchao , Zhong Jingtao , Shi Xuetao , Zhao Lei , Li Hao , Ma Ying 
Published: February 2024

BackgroundThe synergistic effectiveness of combining immune checkpoint inhibitors with targeted therapies has shown promise in improving the conversion rate for unresectable hepatocellular carcinoma (HCC) patients to a potentially resectable status. However, the efficacy of this approach in the context of HCC with extrahepatic metastasis remains to be conclusively determined.Case presentationWe report a rare case of advanced HCC with extrahepatic metastasis who achieved long-term survival by a combination of systemic therapy (sintilimab and sorafenib) followed by laparoscopic hepatectomy. A 63-year-old man presented at our hospital with discomfort on the right side of his waist. An enlarged right hepatic lobe mass was subsequently revealed by CT scan. The patient’s medical history, including a prior infection with hepatitis B virus, cirrhosis of the liver and an alpha-fetoprotein (AFP) level measuring 41.28 ng/ml substantiated the clinical diagnosis of HCC. On October 30th, 2019, the patient received 200 mg sintilimab intravenously (q3w) plus 200–400 mg BID sorafenib orally, along with antiviral therapy. After six cycles, his disease achieved partial response (PR). On April 26th, 2021, He underwent a laparoscopic hepatectomy. The patient achieved a sustained period of no evidence of disease for 2.5 years and with drug-free survival for 2 years after the resection. His current overall survival is estimated at approximately 4 years.ConclusionsThis case highlights the potential of combining sintilimab and sorafenib in transforming HCC with extrahepatic metastasis into a condition amenable to surgical resection, suggesting that this treatment approach, followed by surgery, may lead to complete remission.
Combined intravenous ribavirin and recombinant human interferon α1b aerosol inhalation for adenovirus pneumonia with plastic bronchitis in children: a case report and review of literature
Authors: Lin Liangkang , Tang Maoting , Li Deyuan , Fei Haotian , Zhang Haiyang 
Published: February 2024

BackgroundHuman adenovirus (HAdV) infections in children can lead to profound pulmonary injury and are frequently associated with severe complications, particularly in cases concomitant with plastic bronchitis. Managing this condition presents significant challenges and carries an exceptionally high fatality rate. Regrettably, there are currently no specific antiviral agents that have demonstrated efficacy in treating severe adenovirus pneumonia in children.Case presentationWe report a 10-month-old infant suffering from severe adenovirus pneumonia combined with plastic bronchitis (PB). He received intravenous ribavirin combined with recombinant human interferon α1b (INFα1b) aerosol inhalation and his condition eventually improved. No side effects occurred during the treatment, and the long-term prognosis was favorable.ConclusionIn this case, the combination therapy of intravenous ribavirin and INFα1b seems to have contributed to the resolution of illness and may be considered for similar cases until stronger evidence is generated.
Neuroprotective effects of a novel peptide through the Rho-integrin-Tie2 and PI3K/Akt pathways in experimental autoimmune encephalomyelitis model
Authors: Zhou Wen , Qu Han , Fu Xiao-Xiao , Xu Miao-Miao , Li Qiang , Jiang Yuan , Han Shu 
Published: February 2024

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvβ3 and α5β1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model.Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE.Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvβ3, and α5β1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16.Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.
Emerging antioxidant therapies in Friedreich’s ataxia
Authors: Edzeamey Fred Jonathan , Ramchunder Zenouska , Pourzand Charareh , Anjomani Virmouni Sara 
Published: February 2024

Friedreich’s ataxia (FRDA) is a rare childhood neurologic disorder, affecting 1 in 50,000 Caucasians. The disease is caused by the abnormal expansion of the GAA repeat sequence in intron 1 of the FXN gene, leading to the reduced expression of the mitochondrial protein frataxin. The disease is characterised by progressive neurodegeneration, hypertrophic cardiomyopathy, diabetes mellitus and musculoskeletal deformities. The reduced expression of frataxin has been suggested to result in the downregulation of endogenous antioxidant defence mechanisms and mitochondrial bioenergetics, and the increase in mitochondrial iron accumulation thereby leading to oxidative stress. The confirmation of oxidative stress as one of the pathological signatures of FRDA led to the search for antioxidants which can be used as therapeutic modality. Based on this observation, antioxidants with different mechanisms of action have been explored for FRDA therapy since the last two decades. In this review, we bring forth all antioxidants which have been investigated for FRDA therapy and have been signed off for clinical trials. We summarise their various target points in FRDA disease pathway, their performances during clinical trials and possible factors which might have accounted for their failure or otherwise during clinical trials. We also discuss the limitation of the studies completed and propose possible strategies for combinatorial therapy of antioxidants to generate synergistic effect in FRDA patients.
Fatty acid unsaturation improves germination of upland cotton (Gossypium hirsutum) under cold stress
Authors: Dhaliwal Lakhvir Kaur , Shim Junghyun , Auld Dick , Angeles-Shim Rosalyn B. 
Published: February 2024

IntroductionThe level of fatty acid unsaturation in seeds is one of the major determinants of cold germination ability, particularly in oilseeds. The presence of cis double bonds in unsaturated fatty acids creates bends that lowers their melting temperatures compared to saturated fatty acids. Unsaturated fatty acids with low melting points mobilize faster at low temperatures providing seeds with sufficient energy for germination.MethodologyTo investigate the effects of fatty acid unsaturation on the ability of cotton seeds to germinate under cold conditions, four recombinant inbred lines (RILs) of cotton with unique fatty acid profiles were evaluated using a set of developmental and biochemical assays at 12°C (critically low temperature), 15°C (cardinal minimum temperature) and 30°C (optimum temperature). Furthermore, whole seed lipidome profiling using liquid chromatography with mass spectrometry was done to compare the lipid compositional changes at 12°C and 30°C after imbibing cotton seeds of all the six genotypes for 0 hours, 3 hours and 6 hours.Results and discussionThe RILs with higher unsaturation/saturation ratios registered robust germination performance, lower solute leakage, and optimum water uptake rates under cold stress. Imbibition at 30°C for 8 hours before cold exposure significantly improved the germination of cold sensitive genotypes, indicating that the first few hours of water uptake are critical for cold stress. Whole seed lipidome profiling of all the genotypes specifically associated cold germination ability with higher unsaturation levels of phospholipids during early imbibition. The presence of cis double bonds in phospholipids creates kinks that maintain the fluidity of cell membranes under low temperature. Membrane flexibility under cold conditions is essential for facilitating key germination events including membrane organization and respiration. The current results highlight the importance of fatty acid composition in cold germination ability of upland cotton.
Emotional and behavioral features associated with subclinical hypothyroidism in children and adolescents with Down syndrome
Authors: Fucà Elisa , Costanzo Floriana , Galassi Paolo , Celestini Laura , Villani Alberto , Valentini Diletta , Vicari Stefano 
Published: February 2024

BackgroundSubclinical hypothyroidism (SH) is particularly frequent in individuals with Down syndrome (DS). Despite the amount of evidence suggesting SH is associated with psychopathological symptoms and sleep problems in general population, poor is known about the emotional and behavioral features associated with SH in children with DS.ObjectiveThe first aim of the current study was to investigate differences in emotional and behavioral profiles between a group of children with DS exhibiting co-occurring SH and a group of age and BMI-matched children with DS without co-occurring SH. The second aim of the present study was to investigate differences in sleep disturbances between these groups.MethodsWe included in this retrospective study 98 participants with DS aged 3–18 years with the aim to explore differences in emotional/behavioral problems as well as in sleep difficulties between children with DS with or without co-occurring SH.ResultsParticipants with co-occurring SH exhibited significantly higher scores at several scales of the Conners’ Parent Rating Scales Long Version – Revised. However, they did not exhibit more sleep problems than control group.ConclusionThese results provide specific indications for psychological and neuropsychiatric evaluation of children with DS with suspected or diagnosed SH, highlighting the importance of a multidisciplinary approach in clinical care for children and adolescents with DS.
Attachment networks in young adults
Authors: Carli Lucia L. , Alì Paolo Alessandro , Anzelmo Elena , Caprin Claudia , Crippa Franca , Gallucci Marcello , Moioli Loredana , Traficante Daniela , Feeney Judith A. 
Published: February 2024

IntroductionThis study investigated attachment networks in a sample of Italian young adults. Attachment networks were defined in terms of attachment functions, attachment strength, the presence of a primary figure, and full-blown attachments.MethodParticipants were 405 young adults, and we studied the effects of the demographic variables of gender, romantic status (whether single, involved in a romantic relationship for less or more than 24 months) and employment (whether university students or workers) on the structure of attachment networks. Participants were asked to answer the WHO-TO questionnaire, and derived indexes were analyzed using mixed ANOVAs, linear and logistic regression techniques.ResultsResults indicated that while friends still had great importance in the network, partners were acquiring increasing relevance; at the same time, parents, and particularly mothers, remained central figures, particularly for the secure base function. Regarding the demographic variables, we observed that women reported stronger bonds with their mothers than men did, while the importance of friends was higher for men than for women. Additionally, our study supports previous findings underlining the importance of romantic partners in this phase of life, with participants involved in romantic relationships for longer than 24 months showing a fully developed attachment bond with their partners. Finally, for workers, the transfer of functions from the family-of-origin to external figures seemed to be fostered.DiscussionIn conclusion, young Italian young adults go through a phase of intensive restructuring of attachment bond networks, particularly in relation to the consolidation of romantic relationships and work commitments.
Which types of social support matter for Black sexual minority men coping with internalized homophobia? Findings from a mediation analysis
Authors: Dawes Hayden C. , Eden Tiffany M. , Hall William J. , Srivastava Ankur , Williams Denise Yookong , Matthews Derrick D. 
Published: February 2024

BackgroundMinority stress theory views social support as a protective factor against the effects of minority-specific stressors like internalized homophobia (IH) on mental health in sexual minority populations. However, much of the empirical validation of this theory has been conducted within predominantly White samples, resulting in a limited understanding of how the theory applies to Black sexual minority individuals. Current examinations of social support fail to capture the nuances of how Black sexual minority men may access support systems differently, resulting in a need to investigate how social support, IH, and mental health operate for Black sexual minority men. This study examined relationships between IH, depression, and different types of social support (i.e., family, friends, Black community, gay community) using a mediation model.MethodsWe used data from the POWER (Promoting Our Worth Equity and Resilience) Study, which recruited Black sexual minority men at Black Pride events across six cities in the United States from 2014 to 2017, to test four mediation pathways concurrently in Stata 17. Participants (N = 4,430) completed a questionnaire assessing a variety of health and life domains, including depression symptoms, internalized homophobia, and social support.ResultsIH was positively associated with depression. Lower levels of family, friend, and Black community support were all positively associated with depression symptoms. Additionally, IH was positively associated with all types of support. Finally, family, friend, and Black community support partially mediated the relationship between IH and depression.Conclusions and implicationsResults suggest that the relationship between social support and depression is complex for Black sexual minority men. Findings suggest family support is an important factor for clinical intervention efforts targeting depression, and that gay community support systems should assess how their environments can better support Black sexual minority men. Overall, findings demonstrate the necessity of future examination of how social support functions differently within Black sexual minority communities.