bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separate and overlapping mechanisms of statistical regularities and salience processing in the occipital cortex and dorsal attention network
Authors: Beffara Bertrand , Hadj‐Bouziane Fadila , Hamed Suliann Ben , Boehler C. Nico , Chelazzi Leonardo , Santandrea Elisa , Macaluso Emiliano 
Published: October 2023

AbstractAttention selects behaviorally relevant inputs for in‐depth processing. Beside the role of traditional signals related to goal‐directed and stimulus‐driven control, a debate exists regarding the mechanisms governing the effect of statistical regularities on attentional selection, and how these are integrated with other control signals. Using a visuo‐spatial search task under fMRI, we tested the joint effects of statistical regularities and stimulus‐driven salience. We found that both types of signals modulated occipital activity in a spatially specific manner. Salience acted primarily by reducing the attention bias towards the target location when associated with irrelevant distractors, while statistical regularities reduced this attention bias when the target was presented at a low probability location, particularly at the lower levels of the visual hierarchy. In addition, we found that both statistical regularities and salience activated the dorsal frontoparietal network. Additional exploratory analyses of functional connectivity revealed that only statistical regularities modulated the inter‐regional coupling between the posterior parietal cortex and the occipital cortex. These results show that statistical regularities and salience signals are both spatially represented at the occipital level, but that their integration into attentional processing priorities relies on dissociable brain mechanisms.
Patient‐reported swallowing outcomes after transoral robotic thyroidectomy: Comparison with conventional transcervical thyroidectomy
Authors: Lee Seung Yeol , Ryu Soo Rack , Yun Bo Ram , Ji Yong Bae , Song Chang Myeon , Tae Kyung 
Published: October 2023

AbstractBackgroundThis study aimed to evaluate the swallowing outcomes after transoral robotic thyroidectomy (TORT) and compare them with those of conventional transcervical thyroidectomy.MethodWe enrolled 146 patients who underwent thyroidectomy (73 TORT; 73 conventional approach). We prospectively analyzed swallowing outcomes using the Swallowing Impairment Index‐6 (SIS‐6) questionnaire, a patient‐reported measure, before and 1, 3, and 6 days; 1, 3, and 6 months; and 1 year after surgery. Propensity score‐matched analysis was performed using three covariates: age, sex, and extent of thyroidectomy.ResultsSIS‐6 scores worsened significantly immediately after surgery and progressively recovered 1 year postoperatively in both groups. Propensity score matching generated two matched groups of 22 patients each. In the propensity score‐matched samples, the SIS‐6 scores did not differ between the TORT and conventional groups, except at 1 day postoperatively.ConclusionPatient‐reported swallowing outcomes of TORT were comparable to those of the conventional transcervical procedure.
Dependence of peripheral T‐cell lymphoma on constitutively activated JAK3: Implication for JAK3 inhibition as a therapeutic approach
Authors: Le Kang , Vollenweider Jordan , Han JingJing , Staudinger Nicholas , Stenson Mary , Bayraktar Lara , Wellik Linda E. , Maurer Matthew J. , McPhail Ellen D. , Witzig Thomas E. , Gupta Mamta 
Published: October 2023

AbstractPeripheral T‐cell lymphoma (PTCL) is a clinically heterogeneous group that represents 10%–15% of all lymphomas. Despite improved genetic and molecular understanding, treatment outcomes for PTCL have not shown significant improvement. Although Janus kinase‐2 (JAK2) plays an important role in myeloproliferative neoplasms, the critical role of JAK isoforms in mediating prosurvival signaling in PTCL cells is not well defined. Immunohistochemical analysis of PTCL tumors (n = 96) revealed high levels of constitutively active JAK3 (pJAK3) that significantly (p < 0.04) correlated with the activation state of its canonical substrate STAT3. Furthermore, constitutive activation of JAK3 and STAT3 positively correlated, at least in part, with an oncogenic tyrosine phosphatase PTPN11. Pharmacological inhibition of JAK3 but not JAK1/JAK2 significantly (p < 0.001) decreased PTCL proliferation, survival and STAT3 activation. A sharp contrast was observed in the pJAK3 positivity between ALK+ (85.7%) versus ALK‐negative (10.0%) in human PTCL tumors and PTCL cell lines. Moreover, JAK3 and ALK reciprocally interacted in PTCL cells, forming a complex to possibly regulate STAT3 signaling. Finally, combined inhibition of JAK3 (by WHI‐P154) and ALK (by crizotinib or alectinib) significantly (p < 0.01) decreased the survival of PTCL cells as compared to either agent alone by inhibiting STAT3 downstream signaling. Collectively, our findings establish that JAK3 is a therapeutic target for a subset of PTCL, and provide rationale for the clinical evaluation of JAK3 inhibitors combined with ALK‐targeted therapy in PTCL.
Exploring therapeutic potential of Woodfordia fruticosa (L.) Kurz leaf and bark focusing on antioxidant, antithrombotic, antimicrobial, anti‐inflammatory, analgesic, and antidiarrheal properties
Authors: Rahman Md. Mahfuzur , Soma Mahfuza Afroz , Sultana Nahid , Hossain Md. Jamal , Sufian Md. Abu , Rahman M. Oliur , Rashid Mohammad A. 
Published: October 2023

AbstractBackground and AimsThe study aimed to evaluate the pharmacological properties of methanolic extracts of leaves and barks of Woodfordia fruticosa (L.) Kurz (family: Lythraceae) focusing on antioxidant, thrombolytic, anti‐inflammatory, antibacterial, analgesic, and antidiarrheal effects.Methods1,1‐Diphenyl‐2‐picrylhydrazyl (DPPH) free radical scavenging assay, clot lysis, disc diffusion, and membrane stabilizing methods were employed to assess in vitro antioxidant, thrombolytic, antibacterial, and anti‐inflammatory properties of the leaf and bark methanolic extracts (ME) of W. fruticosa and different organic solvents, that is, petroleum ether (PE), dichloromethane (DCM), chloroform (CL), and aqueous (AQ) fractions. In addition, in vivo central and peripheral analgesic and antidiarrheal activities of both crude extracts were evaluated at two doses (200 and 400 mg/kg of body weight [bw]).ResultsAll the extracts and fractions showed promising antioxidant properties by scavenging DDPH free radicals with IC50 of 6.11–20.79 μg/mL. AQ fraction (41.24%) of leaves and ME (44.90%) of bark exerted notable in vitro thrombolytic activity. The CL fraction of leaves and AQ fraction of the bark showed 43.16% and 45.37% inhibition of RBC hemolysis, respectively, compared to the inhibition of RBC hemolysis by aspirin in a hypotonic‐induced membrane stabilizing assay. Besides, both extracts were observed to provide significant (p < 0.001) central and peripheral analgesic responses at both doses of 200 and 400 mg/kg bw. Furthermore, both doses of bark extract (p < 0.001) and the 400 mg/kg bw of leaf extract (p < 0.05) were observed to possess statistically significant antidiarrheal activity. Additionally, in an in vivo acute toxicity investigation, both extracts had a median lethal dose (LD50) greater than 5000 mg/kg bw, indicating their safety level.ConclusionThe current study proves the ethnomedicinal uses of W. fruticosa; however, further studies are required for phytochemical screening to isolate the responsible bioactive compounds and discover the lead molecules from the plant species.
Does organizational support affect the governance performance of the farm irrigation system? Evidence from the Yellow River basin in China
Authors: Fu Yangqi , Zhu Yuchun 
Published: October 2023

AbstractThe engagement of farmers in the governance of farm irrigation systems is crucial for meeting irrigation demands and enhancing farm productivity. Theoretically, grassroots organizations' concerns and support for farmers will encourage them to participate in the activities of the organization, thus improving the management performance of the irrigation system. This paper examines the influence of organizational aid on the governance of agricultural irrigation systems using field survey data in the Yellow River basin, China. The seemingly unrelated regression model is used to explore the group disparities under distinct organizational circumstances and farm household characteristics. The study demonstrates that the software and hardware support provided by organizations can promote improved management performance of irrigation systems. In addition, considering the heterogeneity of organizational environments, such support is more conducive to enhancing the governance of systems in organizations with more cooperative atmospheres and higher degrees of fairness. From the perspective of the heterogeneity of system users, providing organizational support to growers with a low degree of nonagricultural transformation and labour shortage is more conducive to improving governance performance. Consequently, establishing an excellent organizational atmosphere and targeting organizational support to farmers is a viable means to optimize the governance of irrigation systems.
Differences in Serum Concentrations of and Responses to Generic Verapamil in the Elderly
Authors: Carter Barry L. , Noyes Margaret A. , Demmler Richard W. 
Published: October 2023

Study Objective. To determine if there are greater differences in bioavailability of generic verapamil at steady state in elderly patients than in healthy young subjects.Design. Double‐blind, randomized, three‐way crossover study.Setting. Clinical research center at a general teaching hospital.Subjects. Eight young, healthy subjects between ages 18 and 45 years, and eight elderly, hypertensive patients over 65 years of age.Interventions. Each participant was randomly assigned to receive brand‐name verapamil or one of two generic preparations. Young subjects received each of the three preparations 80 mg twice/day for 7 days separated by a 1‐week washout. Elderly patients took the three preparations for 21 days. Serum drug levels and blood pressure were measured and electrocardiograms performed 13 times after the last dose of drug.Main Results. In young subjects, the pharmacokinetics and pharmacodynamics of the three preparations were nearly identical. There was, however, a great deal of variability in the bioavailability of the generic products. In the elderly patients, one generic product had a maximum serum concentration and area under the curve that were 77% and 43% greater, respectively, than the brand‐name product (p<0.02). Assessments of bioequivalency (based on confidence intervals) demonstrated that this generic drug's bioavailability was from 4–118% and peak serum concentration from 10–139% greater than the brand‐name drug. This was associated with greater prolongation of the PR intervals.Conclusions. A generic verapamil product that is bioequivalent in young subjects may not be bioequivalent in elderly subjects. Testing of drugs with complex pharmacokinetics in young subjects may not reliably predict the clinical outcomes in elderly hypertensive patients.
Institution‐Specific Patterns of Infection and Gram's Stain as Guides for Empiric Treatment of Patients Hospitalized With Typical Community‐Acquired Pneumonia
Authors: Belliveau Paul , Hickingbotham Nancy , Maderazo Eufronio G. , Mazens‐Sullivan Mary , Robinson Ann 
Published: October 2023

Study Objective. To determine the appropriateness of cefazolin as empiric treatment of typical, as opposed to atypical, bacterial community‐acquired pneumonia at our institution.Design. Combination of retrospective chart review and prospective determination of microbial susceptibilities and cefazolin‐associated cost savings.Setting. General acute‐care referral hospital.Patients. We evaluated the charts of patients discharged with a diagnosis of community‐acquired pneumonia over a 10‐year period. Gram's stains and culture results of sputum samples processed over 2 months were analyzed to determine the ability of the stains to predict positive Haemophilus influenzae cultures. The susceptibility and β‐lactamase status of clinical isolates of H. influenzae were determined. Cost savings of cefazolin as empiric treatment for community‐acquired pneumonia were evaluated.Measurements and Main Results. The frequency of H. influenzae pneumonia at our institution was 15% of the three major bacterial community‐acquired pneumonias. Gram's stain was highly accurate in predicting the presence or absence of Haemophilus sp in sputum. Five patients had positive outcomes with cefazolin treatment despite being diagnosed with H. influenzae pneumonia. The organism isolates demonstrated intermediate sensitivity to cefazolin and 85% were β‐lactamase negative. Our program that encourages empiric use of cefazolin over cefuroxime for typical bacterial community‐acquired pneumonia has allowed a modest projected annual cost savings of $24,000.Conclusions. We concluded that when Gram's stain of sputum does not show Haemophilus sp in patients with typical bacterial community‐acquired pneumonia, empiric treatment with cefazolin is appropriate and results in cost savings.
The Acrosome Reaction‐Inducing Effect of Human Follicular and Oviductal Fluid
Authors: de JONGE CHRISTOPHER J. , BARRATT CHRISTOPHER L. R. , RADWANSKA EWA , COOKE IAN D. 
Published: October 2023

ABSTRACTThe human sperm acrosome reaction (AR) can be induced in vitro by a variety of naturally occurring and synthetic compounds. The present investigation determined the effect of human natural cycle periovulatory follicular (hFF) and oviductal fluids (hOF) on the human sperm AR in dose—response fashion using the synchronous AR assay. When hFF (30% v/v) or hOF (40% v/v) was added to non‐capacitated spermatozoa, no significant (P > 0.05) increase in the % AR was detected in comparison to the non‐treatment control. When either of these compounds was added (10%, 20%, and 30% v/v hFF; 20%, 30%, and 40% v/v hOF) to capacitated spermatozoa (3 hour incubation), a significant (P < 0.05) stimulation of the AR was detected. Bovine oviductal fluid (bOF) was tested (20%, 30%, and 40% v/v) to determine if it might have an effect similar to hOF. In contrast to hOF, the highest concentration of bOF (40% v/v) tested failed to stimulate a significant (P > 0.05) increase in the % AR of capacitated spermatozoa in comparison to control. Inhibitors of protein kinases A (KT5720) and C (calphostin C) were tested to determine their effects on the hFF‐induced AR. In comparison to hFF treatment alone, the kinase A inhibitor KT5720 (50 nM, 100 nM) prevented hFF (20%) stimulation of the AR when added at the end of the capacitation period and 5 minutes prior to the addition of inducer. Similarly, the kinase C inhibitor calphostin C (50 nM, 100 nM) prevented hFF (20%) stimulation of the AR. The present data demonstrate that periovulatory hFF and hOF stimulate the human sperm AR. hFF appears to stimulate the AR by activating multiple signal transduction pathways.
Histone acetylation regulates ORMDL3 expression‐mediated NLRP3 inflammasome overexpression during RSV‐allergic exacerbation mice
Authors: Cheng Qi , He Fanghan , Zhao Wenqi , Xu Xianhong , Shang Yunxiao , Huang Wanjie 
Published: October 2023

AbstractWhether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1‐like protein 3 (ORMDL3) and lead to NOD‐like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV‐induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12‐SV40 2B (BEAS‐2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV‐bronchiolitis follow‐up. In BEAS‐2B, ORMDL3‐induced NLRP3 inflammasome expression. BEAS‐2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3‐small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.
Salmonella engages CDC42 effector protein 1 for intracellular invasion
Authors: Bandyopadhyay Sheila , Zhang Xiao , Ascura Andrea , Edelblum Karen L. , Bonder Edward M. , Gao Nan 
Published: October 2023

AbstractHuman enterocytes are primary targets of infection by invasive bacterium Salmonella Typhimurium, and studies using nonintestinal epithelial cells established that S. Typhimurium activates Rho family GTPases, primarily CDC42, to modulate the actin cytoskeletal network for invasion. The host intracellular protein network that engages CDC42 and influences the pathogen's invasive capacity are relatively unclear. Here, proteomic analyses of canonical and variant CDC42 interactomes identified a poorly characterized CDC42 interacting protein, CDC42EP1, whose intracellular localization is rapidly redistributed and aggregated around the invading bacteria. CDC42EP1 associates with SEPTIN‐7 and Villin, and its relocalization and bacterial engagement depend on host CDC42 and S. Typhimurium's capability of activating CDC42. Unlike CDC42, CDC42EP1 is not required for S. Typhimurium's initial cellular entry but is found to associate with Salmonella‐containing vacuoles after long‐term infections, indicating a contribution to the pathogen's intracellular growth and replication. These results uncover a new host regulator of enteric Salmonella infections, which may be targeted to restrict bacterial load at the primary site of infection to prevent systemic spread.
Appendicular lean mass index changes in patients with Duchenne muscular dystrophy and Becker muscular dystrophy
Authors: Wong Brenda L. , Summer Suzanne , Horn Paul S. , Rutter Meilan M. , Rybalsky Irina , Tian Cuixia , Shellenbarger Karen C. , Kalkwarf Heidi J. 
Published: October 2023

AbstractIntroductionMutations in the 79 exons of the dystrophin gene result in muscle wasting and weakness of varying clinical severity, ranging from severe/typical Duchenne muscular dystrophy (DMD) to intermediate DMD and mild Becker muscular dystrophy (BMD), depending on the frameshift of the mutation. We previously reported that males with DMD have progressively declining appendicular lean mass (ALM) and ALM index (ALMI) with age and worsening functional motor ability compared with healthy controls. These indices have not been studied in patients with intermediate DMD and BMD phenotypes and across DMD genotypes. In this study, we compared age‐related trajectories of ALM and ALMI of patients who had (1) BMD without functional mobility deficits with patients who had DMD at different stages of disease and healthy controls; (2) a DMD intermediate phenotype with patients who had a typical DMD phenotype; and (3) DMD categorized by genotype.MethodsWe conducted a retrospective review of ALM and ALMI data from 499 patients (ages 5–23 years) with DMD (466 typical and 33 intermediate) and 46 patients (ages 5–21 years) with BMD (without functional mobility deficits and functional mobility score of 1). Patients were grouped according to age reflecting disease stage (ages 5 to <7, 7 to <10, 10 to <14, and 14 to <20 years) and genotype (mutations in exons 1–30, 31–44, 45–62, and 63–79).ResultsALM and ALMI trajectories of patients with BMD paralleled those of healthy controls until adolescence, in contrast to patients with DMD. ALMI Z‐scores of patients with BMD remained within ±2 SD without decline while those of patients with DMD fell below −2 SD around age 12 years. Patients with BMD had increasing ALM and ALMI with age, with peak accrual between ages 10 to <14 years. ALMI declined after age 14 years for those with intermediate DMD compared with 10 years for patients with typical DMD. Patients with mutations in exons 63–79 had a greater decline in ALMI as compared with those with other genotypes after age 10 years.ConclusionsAge‐related changes in ALMI in patients with BMD and intermediate DMD differ from those with typical DMD, reflecting their clinical phenotypes. ALM and ALMI should be further studied in patients with BMD and DMD subtypes for their potential value as surrogate markers to characterize the severity of BMD and DMD and inform clinical care decisions and clinical trial designs.
Suppressors of cGAS‐STING are downregulated during fin‐limb regeneration and aging in aquatic vertebrates
Authors: Mathavarajah Sabateeshan , Thompson Andrew W. , Stoyek Matthew R. , Quinn T. Alexander , Roy Stéphane , Braasch Ingo , Dellaire Graham 
Published: October 2023

AbstractDuring the early stages of limb and fin regeneration in aquatic vertebrates (i.e., fishes and amphibians), blastema undergo transcriptional rewiring of innate immune signaling pathways to promote immune cell recruitment. In mammals, a fundamental component of innate immune signaling is the cytosolic DNA sensing pathway, cGAS‐STING. However, to what extent the cGAS‐STING pathway influences regeneration in aquatic anamniotes is unknown. In jawed vertebrates, negative regulation of cGAS‐STING activity is accomplished by suppressors of cytosolic DNA such as Trex1, Pml, and PML‐like exon 9 (Plex9) exonucleases. Here, we examine the expression of these suppressors of cGAS‐STING, as well as inflammatory genes and cGAS activity during caudal fin and limb regeneration using the spotted gar (Lepisosteus oculatus) and axolotl (Ambystoma mexicanum) model species, and during age‐related senescence in zebrafish (Danio rerio). In the regenerative blastema of wounded gar and axolotl, we observe increased inflammatory gene expression, including interferon genes and interleukins 6 and 8. We also observed a decrease in axolotl Trex1 and gar pml expression during the early phases of wound healing which correlates with a dramatic increase in cGAS activity. In contrast, the plex9.1 gene does not change in expression during wound healing in gar. However, we observed decreased expression of plex9.1 in the senescing cardiac tissue of aged zebrafish, where 2′3′‐cGAMP levels are elevated. Finally, we demonstrate a similar pattern of Trex1, pml, and plex9.1 gene regulation across species in response to exogenous 2′3′‐cGAMP. Thus, during the early stages of limb‐fin regeneration, Pml, Trex1, and Plex9.1 exonucleases are downregulated, presumably to allow an evolutionarily ancient cGAS‐STING activity to promote inflammation and the recruitment of immune cells.