bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals
Authors: Kim Rebecca G. , Kramer‐Feldman Jonathan , Bacchetti Peter , Grimes Barbara , Burchard Esteban , Eng Celeste , Hu Donglei , Hellerstein Marc , Khalili Mandana 
Published: November 2021

AbstractBackgroundAlcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV.MethodsOne hundred fifty‐three nondiabetic Latino individuals (60 HCV+, 93 HCV−) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow‐up of 1.5 years. Peripheral IR and hepatic IR were measured via steady‐state plasma glucose (SSPG) and endogenous glucose production during a two‐step, 240‐min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time.ResultsOverall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 μU‐mg/kg‐min‐ml, p = 0.04) and HCV status (coef 4.4 μU‐mg/kg‐min‐ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow‐up (coef 5.8 μU‐mg/kg‐min‐ml, p = 0.03).ConclusionsIn this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti‐HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.
Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one‐year extension study
Authors: Maurer Marcus , Giménez‐Arnau Ana , Bernstein Jonathan A. , Chu Chia‐Yu , Danilycheva Inna , Hide Michihiro , Makris Michael , Metz Martin , Savic Sinisa , Sitz Karl , Soong Weily , Staubach Petra , Sussman Gordon , Barve Avantika , Burciu Alis , Hua Eva , Janocha Reinhold , Severin Thomas 
Published: November 2021

AbstractBackgroundLigelizumab, a next‐generation, humanized anti‐immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard‐of‐care therapy.ObjectiveTo evaluate the long‐term safety and re‐treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study.MethodsThis open‐label, single‐arm, long‐term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose‐finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post‐treatment for 48 weeks.ResultsOverall, ligelizumab was well‐tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment‐emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks.ConclusionThe long‐term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re‐treatment efficacy was shown.Trial Registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.
Has the time come to stop routine N‐acetylcysteine treatment in young children in Denmark? A review of 300 suspected paracetamol overdoses in children aged 0–6 years
Authors: Gade Christina , Bøgevig Søren , Daoud Alaa , Mathiesen Pernille R. , Christensen Mikkel B. , Dalhoff Kim P. , Petersen Tonny S. 
Published: November 2021

AbstractAimTo evaluate the prevalence of potentially hepatoxic paracetamol ingestion and associated N‐acetylcysteine treatment in young children suspected of paracetamol poisoning.MethodsA retrospective cohort study of children aged 0–6 years suspected of paracetamol poisoning with a related plasma‐paracetamol measurement in the Capital Region of Denmark in the period 2010–2017. Data from the clinical laboratory system were linked to data from electronic patient records via the unique identification number given to all Danish residents.ResultsOf 297 children included, suspected single paracetamol overdoses were present in 281 (95%). Sixty‐nine per cent were treated with N‐acetylcysteine, and the mean treatment period was 20.3 h (SD 20.8). A maximum of 6 (2%) of the children suspected of single overdose had plasma‐paracetamol concentrations that exceeded the recommended treatment thresholds. No cases of severe hepatotoxicity were registered. Adverse events to N‐acetylcysteine‐treatment were registered in 3 (2%) children including one anaphylactoid reaction (0.5%).ConclusionThis study shows that initiating N‐acetylcysteine as a ‘one size fit all’ treatment regimen in all children aged 0–6 years with a suspected single paracetamol overdose leads to substantial overtreatment. The data support that it is feasible to initiate N‐acetylcysteine within 10 h based on an early plasma‐paracetamol test.
Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment
Authors: Liu Chen‐Hua , Peng Cheng‐Yuan , Kao Wei‐Yu , Yang Sheng‐Shun , Shih Yu‐Lueng , Lin Chin‐Lin , Tsai Meng‐Kun , Lee Chih‐Yuan , Chang Chun‐Chao , Wu Jo‐Hsuan , Liu Chun‐Jen , Su Tung‐Hung , Tseng Tai‐Chung , Chen Pei‐Jer , Kao Jia‐Horng 
Published: November 2021

SummaryBackgroundData are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment‐induced sustained virologic response (SVR) in patients on haemodialysis.AimsTo assess the risk of HCV reinfection among patients on haemodialysis with treatment‐induced SVR.MethodsPatients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct‐acting antiviral (DAA)‐based treatment received follow‐up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12. The low‐risk general population who achieved SVR12 and who underwent the same post‐SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person‐years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups.ResultsWe recruited 374 patients on haemodialysis and 1571 reference patients with a mean post‐SVR12 follow‐up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24. The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09‐0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10‐0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44‐4.38, P = 0.57).ConclusionsThe risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low‐risk general population. HCV microelimination in this special population is feasible once universal screening and scaled‐up treatment are implemented.
The conception of organizational integrity: A derivation from the individual level using a virtue‐based approach
Authors: Fuerst Madeleine J. , Luetge Christoph 
Published: November 2021

AbstractThis paper extends previous attempts at understanding the nature of organizational integrity and its increasingly important role for companies which, after all, bear a moral and societal responsibility. Interpretations of organizational integrity in business ethics literature incorporate aspects ranging from the behavior of managers and employees to corporate structures and incentive systems. We argue that virtue ethics builds an indispensable framework for understanding the origin of the concept of integrity and transfer these findings to an organizational level. Hence, we first define organizational integrity, and second operationalize it in a closed three‐step process, consisting of morally sound corporate commitments, their transparent institutionalization within the company, and their implementation into actions. We consider the main goal of organizational integrity to be of a preventative investment nature. Organizational integrity is a company investment that translates into avoiding fines for potential violations of the law or ethical missteps, as well as an investment in the company’s reputation. In turn, organizational integrity can protect a company from disruptions that can threaten its existence. Defining and operationalizing the concept of organizational integrity provides the foundation for future scientific research and the basis for developing practical guidance for organizations and managers.
Time‐dependent dual effect of NLRP3 inflammasome in brain ischaemia
Authors: Palomino‐Antolin Alejandra , Narros‐Fernández Paloma , Farré‐Alins Víctor , Sevilla‐Montero Javier , Decouty‐Pérez Celine , Lopez‐Rodriguez Ana Belen , Fernández Nuria , Monge Luis , Casas Ana I. , Calzada María José , Egea Javier 
Published: November 2021

BackgroundInflammasomes are cytosolic multiprotein complexes which, upon assembly, activate the maturation and secretion of the inflammatory cytokines IL‐1β and IL‐18. However, participation of the NLRP3 inflammasome in ischaemic stroke remains controversial. Our aims were to determine the role of NLRP3 in brain ischaemia, and explore the mechanism involved in the potential protective effect of the neurovascular unit.MethodsWT and NLRP3 knock‐out mice were subjected to ischaemia by middle cerebral artery occlusion (60 min) with or without treatment with MCC950 at different time points post‐stroke. Brain injury was measured histologically with 2,3,5‐triphenyltetrazolium chloride (TTC) staining.ResultsWe identified a time‐dependent dual effect of NLRP3. While neither the pre‐treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post‐reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose‐dependent manner. Importantly, MCC950 improved the neuro‐motor function and reduced the expression of different pro‐inflammatory cytokines (IL‐1β and TNF‐α), NLRP3 inflammasome components (NLRP3 and pro‐caspase‐1), protease expression (MMP9), and endothelial adhesion molecules (ICAM and VCAM). We observed a marked protection of the blood–brain barrier (BBB), which was also reflected in the recovery of the tight junction proteins (ZO‐1 and Claudin‐5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration.ConclusionsThese findings suggest that post‐reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood–brain barrier in cerebral ischaemia with potential clinical translation.
PD‐L1 and PD‐L2 expression status in relation to chemotherapy in primary and metastatic esophageal squamous cell carcinoma
Authors: Okadome Kazuo , Baba Yoshifumi , Yasuda‐Yoshihara Noriko , Nomoto Daichi , Yagi Taisuke , Toihata Tasuku , Ogawa Katsuhiro , Sawayama Hiroshi , Ishimoto Takatsugu , Iwatsuki Masaaki , Iwagami Shiro , Miyamoto Yuji , Yoshida Naoya , Watanabe Masayuki , Komohara Yoshihiro , Baba Hideo 
Published: November 2021

AbstractImmune checkpoint inhibitors have shown efficacy in various cancers. Although programmed death ligand 1/2 (PD‐L1/L2) expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD‐L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD‐L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinomas and PD‐L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD‐L1/L2 expression and PD‐L1/L2‐related pathways in vitro. We also examined PD‐L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD‐L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD‐L2 expression showed no significant difference between patient groups. Cisplatin increased PD‐L1 expression in cancer cell lines in vitro, but decreased PD‐L2 in some cell lines. The effects of cisplatin on phosphorylated signal transducer and activator of transcription 1/3 (pSTAT1/3) also differed depending on cell lines. Fluorouracil increased PD‐L1 and PD‐L2 expression. PD‐L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD‐L1/L2 expression may be altered by preoperative chemotherapy, and PD‐L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one‐time evaluation is not sufficient to evaluate PD‐L1/L2 expression as a biomarker in esophageal cancer.
Micronutritional supplementation with a holoBLG‐based FSMP (food for special medical purposes)‐lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect
Authors: Afify Sheriene Moussa , Regner Andreas , Pacios Luis F. , Blokhuis Bart R. , Jensen Sebastian A. , Redegeld Frank A. , Pali‐Schöll Isabella , Hufnagl Karin , Bianchini Rodolfo , Guethoff Sonja , Kramer Matthias F. , Fiocchi Alessandro , Dvorak Zdenek , Jensen‐Jarolim Erika , Roth‐Walter Franziska 
Published: November 2021

AbstractBackgroundPreviously, the protective farm effect was imitated using the whey protein beta‐lactoglobulin (BLG) that is spiked with iron‐flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin‐iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.MethodsBinding of iron‐catechin into BLG was confirmed by spectroscopy and docking calculations. Serum IgE binding of children allergic or tolerating milk was assessed to loaded (holo‐) versus empty (apo‐) BLG and for human mast cell degranulation. BLG and Bet v 1 double‐sensitized mice were orally treated with the holoBLG or placebo lozenge, and immunologically analysed after systemic allergen challenge. Human PBMCs of pollen allergic subjects were flow cytometrically assessed after stimulation with apoBLG or holoBLG using catechin‐iron complexes as ligands.ResultsOne major IgE and T cell epitope were masked by catechin‐iron complexes, which impaired IgE binding of milk‐allergic children and degranulation of mast cells. In mice, only supplementation with the holoBLG lozenge reduced clinical reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen presentation. In allergic subjects, stimulation of PBMCs with holoBLG led to a significant increase of intracellular iron in circulating CD14+ cells with significantly lower expression of HLADR and CD86 compared to their stimulation with apoBLG.ConclusionThe FSMP lozenge targeted antigen presenting cells and dampened immune activation in human immune cells and allergic mice in an antigen‐non‐specific manner, thereby conferring immune resilience against allergic symptoms.
Role of sequential chemical peel in cutaneous amyloidosis: a pilot case series
Authors: Divyalakshmi C. , Hazarika N. , Barnwal S. 
Published: November 2021

Summary
Cutaneous amyloidosis can be a part of a systemic disease or can result from a localized process limited to the skin. It usually presents as pruritic hyperpigmented macules, papules or nodules, which are notoriously resistant to treatment. We performed a hospital-based pilot case series to assess the efficacy and safety of sequential salicylic acid (SA) and glycolic acid (GA) chemical peels. Patients underwent sequential chemical peel therapy with SA 20% and GA 35% used alternately each week for a total of 6 weeks. At subsequent follow-up visits, good clinical outcome and long-term maintenance was observed. This study highlights the promising role of chemical peels in this difficult and distressing disorder.
Epithelioid and clear‐cell variant of Kaposi sarcoma: A rare histopathologic subtype
Authors: Yim Kaitlyn M. , Liang Tom , Gnass Esteban , DeClerck Brittney 
Published: November 2021

AbstractKaposi sarcoma is a malignant vascular tumor consisting of multiple clinical subtypes and varying histopathologic patterns. We report a case of a 53‐year‐old African‐American male with HIV/AIDS who presented multiple times with skin nodules, pain, and edema in his lower extremities, secondary to recurrent Kaposi sarcoma. The patient was treated with two courses of liposomal doxorubicin with improvement, but his symptoms recurred a third time. A biopsy specimen of one of the nodules showed prominent neoplastic cells of epithelioid morphology, some with clear‐cell change, appearing to form rudimentary vessels in the superficial dermis. Further inspection of the deeper dermis revealed more classic findings of Kaposi sarcoma, including admixed spindle cells, poorly defined vessels, scattered apoptotic bodies, entrapped collagen bundles, and extravasated erythrocytes. Both the epithelioid and classic portions of the neoplasm stained positive for CD31 and human herpesvirus 8, supporting a diagnosis of Kaposi sarcoma. Prior to this case, the epithelioid variant of Kaposi sarcoma has been reported only twice in the literature. Recognizing this rare histopathologic variant of Kaposi sarcoma among its other histopathologic patterns may assist in accurate and expedient diagnosis of this well‐recognized disease.
Community banks versus non‐community banks: Post the Great Recession
Authors: Fayman Alex , Chen Su‐Jane , Mayes Timothy 
Published: November 2021

AbstractCommunity banks (CBs), despite holding a fairly small share of US banking assets, provide vital financial services to key segments of the economy and fill a void untapped by larger non‐community banks (Non‐CBs). They face challenges brought on by a fast‐changing banking landscape, evolving technology, and ever‐increasing regulatory burden. To remain competitive and to gain scale‐related efficiencies, CBs have been seeking mergers even as greater institutional size causes a departure from the classical relationship‐based business model. This study examines performance of US CBs and Non‐CBs post the Great Recession to reveal how size of these institutions may affect their business operations. Empirical findings show that CBs, compared with their larger counterparts, tend to maintain higher levels of liquidity and lower levels of capital, and demonstrate a greater dependence on core deposits, confirming that CBs focus on deposit taking and soft information‐based lending strategies. Furthermore, this study suggests that CBs should not be considered a homogenous group operating under a singular business model and cautions that regulatory dialectics aimed at the banking industry should not employ a one‐size‐fits‐all approach.
Changes in reach‐to‐grasp behaviour over the course of training in rats
Authors: Parmiani Pierantonio , Lucchetti Cristina , Franchi Gianfranco 
Published: November 2021

AbstractOne complex task involving sequence of movements and movement refinement in the rat is the single‐pellet reaching task, comprising orientation, transport and withdrawal in sequence. In turn, orientation comprises front wall detection, slot localization and nose poke until reach start. Video recordings of a rat in the reaching box highlighted three stages of temporal training: start of training (ST), forepaw dominance appearance (D) and fully trained (T). Regarding orientation, ST versus D and T presented a significant smaller frequency of approach to the front wall and a significant higher number of whisker cycles and nose touches during slot localization, involving a significant longer Orientation. At the ST stage, 44% of the trials were interrupted after nose poke, and poke took place at significant higher level from the shelf. The shelf was identified only when short whiskers contacted it, but the tongue and both forepaws were used without distinction to reach and grasp the pellet until a forepaw emerged as dominant at D stage. Regarding the temporal features of transport and withdrawal, comparing the D versus T stage revealed a significant longer duration. Finally, successes were significantly higher in T respect to D, meaning that after dominance emergence, more training was still necessary to improve reaching/grasping performance. This study provides evidence that, during training, the rats develop a strategy to obtain the pellets and then refine their movement pattern.