bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy
Authors: Zhou Juan , Tan Yingzheng , Hu Lingli , Fu Jingli , Li Dan , Chen Jun , Long Yunzhu 
Published: October 2022

AbstractBackground and AimRifampicin is the most common pathogenic factor in anti‐tuberculosis drug‐induced liver injury (AT‐DILI), the mechanisms that it promotes hepatocyte damage in AT‐DILI are not yet to be thoroughly elucidated. In this study, we investigated the potential molecular mechanisms for ferroptosis involving rifampicin hepatotoxicity.MethodsAnimal and cell injury models of rifampicin were constructed, and the toxicity of rifampicin was assessed by physicochemical staining and cell viability assay. Next, flow cytometry was employed to detect changes in ferroptosis‐related markers, and Western blotting was used to detect protein expression. Then, the important role of autophagy and ferroptosis was verified with small molecule compound intervention.ResultsWe found that ferritinophagy‐induced ferroptosis participates in the toxicity of rifampicin, and the mechanism is that rifampicin precisely activates high‐throughput autophagy, which leads to the massive degradation of ferritin and the increase of free iron. Moreover, rifampicin exhibited conspicuous inhibition of Human 71 kDa heat shock cognate protein (HSPA8) that is intimately associated with Microtubule‐associated protein light chain 3 isoform B (LC3B) expression, in turn, HSPA8 inducer attenuated intracellular autophagy flux. Of note, inducing HSPA8 or inhibition of autophagy and ferroptosis considerably relieved the hepatotoxicity of rifampicin in mouse model.ConclusionsThe present study highlights the crucial roles of the HSPA8 and autophagy in ferroptotic cell death driving by rifampicin, particularly illumines multiple promising regulatory nodes for therapeutic interventions in diseases involving AT‐DILI.
Clinical efficacy and mechanism of transcutaneous neuromodulation on ineffective esophageal motility in patients with gastroesophageal reflux disease
Authors: Ma Yimin , Cai Rencheng , Liu Zhengqing , Zou Xiaoping , Qiao Zhenguo 
Published: October 2022

AbstractBackgroundEsophageal motility disorder is one of the pathogenesis of gastroesophageal reflux disease (GERD). The clinical and functional relationship between the ineffective esophageal motility (IEM) and GERD have been found. PPI is a widely used drug of this diaease, but some patients have poor efficacy. The purpose of this study was to investigate the efficacy and possible mechanism of Transcutaneous Neuromodulation in these patients.MethodsFifty‐six patients with GERD with IEM were enrolled and randomly divided into two groups, one group was TN ST‐36 group, the other group was sham TN group. The GERD questionnaire (GerdQ), quality of life score, MOS item short from health survey (SF‐36), Hospital Anxiety and Depression Scale (HADS) were used to assess the severity of symptoms. High‐resolution esophageal manometry (HRM) test was performed to assess low esophageal sphincter (LES) pressure and distal contractile integral (DCI). The heart rate variability (HRV) test was performed to assess autonomic nervous function.Key ResultsCompared with sham TN, chronic TN treatment decreased the GERD‐Q score (p < 0.001). The anxiety score (p = 0.058) and depression score (p = 0.156) were decreased, but there were no statistical differences. Chronic TN treatment also significantly improved the quality of life of patients, mainly in physical function, physical pain, overall health, vitality, social function, emotional function, and mental health. Acute TN treatment increased the DCI (p < 0.001) and LES pressure (p < 0.001) significantly and decreased the combined percentage of failed and weak peristalsis (p < 0.001). Concurrently, acute TN enhanced vagal activity (p < 0.001).Conclusions and InferencesIEM is an important link in the pathogenesis of GERD. Chronic TN treatment can significantly improve the clinical symptoms of patients. Acute TN treatment can significantly increase LES pressure and DCI and reduce the frequency of esophageal lost peristalsis and weak peristalsis. The improvement of esophageal motility in GERD patients with IEM by TN treatment may be related to the regulation of autonomic nervous function.
Xylem hydraulics strongly influence the niche differentiation of tree species along the slope of a river valley in a water‐limited area
Authors: Zhang Chi , Khan Attaullah , Duan Chun‐Yang , Cao Yu , Wu De‐Dong , Hao Guang‐You 
Published: October 2022

AbstractXylem hydraulic characteristics govern plant water transport, affecting both drought resistance and photosynthetic gas exchange. Therefore, they play critical roles in determining the adaptation of different species to environments with various water regimes. Here, we tested the hypothesis that variation in xylem traits associated with a trade‐off between hydraulic efficiency and safety against drought‐induced embolism contributes to niche differentiation of tree species along a sharp water availability gradient on the slope of a unique river valley located in a semi‐humid area. We found that tree species showed clear niche differentiation with decreasing water availability from the bottom towards the top of the valley. Tree species occupying different positions, in terms of vertical distribution distance from the bottom of the valley, showed a strong trade‐off between xylem water transport efficiency and safety, as evidenced by variations in xylem structural traits at both the tissue and pit levels. This optimized their xylem hydraulics in their respective water regimes. Thus, the trade‐off between hydraulic efficiency and safety contributes to clear niche differentiation and, thereby, to the coexistence of tree species in the valley with heterogeneous water availability.
Posterior delta/theta EEG activity as an early signal of Stroop conflict detection
Authors: Haciahmet Céline C. , Frings Christian , Beste Christian , Münchau Alexander , Pastötter Bernhard 
Published: October 2022

AbstractThe conflict monitoring theory postulates that conflict detection is initiated in the anterior cingulate cortex (ACC), indexed by midfrontal theta oscillations in the electroencephalogram (EEG). Recent research suggested that distractor detection (in the Eriksen flanker task) can be initiated relatively early by attentional control processes in the occipital lobe. Whether attentional control is also involved in the detection of stimulus–response overlapping conflict in the Stroop task is yet unclear. In the present study, we analyzed EEG time‐frequency data (N = 47) to investigate the contribution of early attentional control processes to the detection of response conflict and semantic conflict in a lateralized version of the color‐word Stroop task. The behavioral results showed significant conflict effects in response times (RT). The EEG results showed a prominent midfrontal response conflict effect in total theta power (4–8 Hz). Importantly, detection of response conflict and semantic conflict was observed in posterior delta/theta power (2–8 Hz), which was lateralized depending on the presentation side of the irrelevant Stroop words. In explorative regression analysis, both the midfrontal and the posterior response conflict effects predicted the size of response conflict errors. These results suggest that attentional control processes in posterior areas contribute to the initiation of response‐conflict detection in the Stroop task. The findings are consistent with the idea of a representational link between stimulus and response features, known as the common coding principle.
Delabeling penicillin and other antibiotic allergies in solid organ transplantation patients
Authors: Ham Young Yoon , Joshi Shyam , Sukerman Ellie 
Published: October 2022

AbstractBackgroundImmunocompromised populations including solid organ transplant (SOT) recipients have a high likelihood of need for antibiotic therapy for treatment of infection as well as for prophylaxis. Antibiotic allergy is commonly reported and often leads to the use of alternative, second‐line antibiotics, which have been associated with poor outcomes, increased adverse effects, and higher cost. Formal allergy assessment and allergy testing can serve as an important antimicrobial stewardship tool in optimizing antibiotic regimens for this patient population.MethodsA PubMed search with relevant keywords was performed. Review of relevant professional society guidelines was also performed.ResultsDocumented penicillin and sulfonamide allergies are common impediments to the treatment and prophylaxis of immunocompromised populations, but are rarely formally evaluated in practice; however, there is evidence that most patients with documented allergy to these antibiotics can, in fact, tolerate penicillins and sulfonamide antibiotics. Implementation of an antibiotic allergy evaluation and testing program has been shown to increase the use of first‐line antibiotics and can be cost saving.ConclusionAntibiotic allergies have significant clinical consequences, especially in immunocompromised populations. Evaluation of these allergies to prevent the avoidance of first‐line antibiotics should be a standard part of the workflow for these patients, prior to transplant. Programs can be tailored to the available personnel and resources of the organization.image
Challenges and opportunities in stewardship among solid organ transplant recipients with Candida auris bloodstream infections
Authors: Vu Christine A. , Jimenez Adriana , Anjan Shweta , Abbo Lilian M. 
Published: October 2022

AbstractBackgroundCandida auris is an emerging nosocomial pathogen worldwide. However, there has been little published on the management of C. auris in solid organ transplant recipients.MethodsA single‐center, retrospective cohort study was conducted to evaluate C. auris bloodstream infections in solid organ transplant recipients between January 2020 and December 2021. Patient‐related and outcomes data were extracted from electronic medical records.ResultsOf the 42 patients identified with C. auris bloodstream infections, five were in solid organ transplant recipients (1 heart, 3 liver, and 1 combined liver‐kidney). The median time to fungemia from hospital admission was 43 days, and the median time to fungemia from transplant was 18 days. All patients received micafungin as initial treatment, at a median of 6 hours from pathogen detection. Four patients achieved blood clearance, two patients had persistent fungemia, and two patients developed secondary complications from hematogenous spread. One patient died, resulting in a mortality rate of 20%.ConclusionsSolid organ transplant recipients are at high risk for developing C. auris bloodstream infections. In order to prevent graft loss and mortality, best practices for the management of C.auris should include rapid screening, diagnosis, and treatment. While echinocandins are considered first‐line, antifungal selection should be based on susceptibilities and site of infection. Data to support routine use of combination therapy are lacking, however there may be a role for refractory cases. Prevention efforts against C. auris infection are especially important given the lack of effective decolonization strategies. For transplant recipients, hospitals should seek opportunities to restore patients' gut microbiome by curtailing unnecessary hospital procedures and inappropriate antimicrobial use. Further research and national guidelines are needed to better direct stewardship in this field.
Antibiotic allergy labels in immunocompromised populations
Authors: Waldron Jamie L. , Trubiano Jason A. 
Published: October 2022

AbstractAntibiotic allergy labels (AALs) are commonly reported, with well‐defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high‐antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta‐lactam (penicillin) allergy and sulfa‐antibiotic (antimicrobial sulfurs) allergy labels.
Machine learning, antimicrobial stewardship, and solid organ transplantation: Is this the future?
Authors: Kherabi Yousra , Messika Jonathan , Peiffer‐Smadja Nathan 
Published: October 2022

AbstractBackgroundThe use of machine learning (ML) in infectious diseases is expanding.ObjectivesThis review aims to provide an overview of the literature on ML for clinical decision support in antimicrobial stewardship in the particular context of solid organ transplantation (SOT).MethodsReferences for this review were identified through searches of MEDLINE/PubMed and Google Scholar databases up to July 2022.ResultsML may improve the prediction of infectious complications and the diagnosis and treatment of infectious diseases in SOT recipients. One of the most studied applications for antimicrobial stewardship is the individual prediction of antimicrobial resistance that could guide the empiric use of anti‐infective treatments. ML may also guide the choice of antimicrobial dose taking into account the interactions with immunosuppressive drugs. The main challenge to the development of ML clinical decision support systems (CDSSs) in SOT is the development of large clinical databases, accessible to all, with good quality, comprehensive, and diversified data. ML‐driven CDSSs are still at an experimental stage, and the education of clinicians about the benefits and limits of ML is essential.ConclusionML could improve antimicrobial stewardship for SOT, but literature on that specific topic is scarce. Future studies are needed to design ML‐CDSS in the particular population of solid organ recipients and report clinical outcomes following use in routine practice.
Integral Transform Solution of Porous Medium Models for Heat Sinks Subject to Periodic Heat Loads
Authors: Lisboa Kleber Marques , Pinheiro Isabela Florindo , Cotta Renato Machado 
Published: October 2022

Abstract
Analysis of the energy transport in thermal microdevices modeled as a porous medium under periodic heat loads is conducted using integral transforms. Coupled eigenvalue problems are employed and a single set of coupled ordinary differential equations conveying all information on the temperature fields in both the solid and fluid phases are reached, allowing for a relatively straightforward treatment of the local thermal nonequilibrium (LTNE) formulation. This characteristic proved instrumental in finding out that the local thermal equilibrium (LTE) hypothesis is inadequate for unsteady problems. The solid phase is shown to have a significant role on inducing thermal lag in the fluid, which may be severe, depending on the dimensions and operational conditions. In general, devices comprised of larger fractions of solid material and with poorer heat transfer characteristics are more prone to having larger thermal lag along them. These conclusions may be relevant to a wide range of applications such as electronics cooling, battery thermal management, solar energy harvesting, among others.
NONLINEAR, HETEROGENEOUS AND MEDIATING EFFECTS OF INSTITUTIONAL OWNERSHIP ON ENTERPRISE INNOVATION: EVIDENCE FROM CHINESE LISTED ENTERPRISES
Authors: CUI ZHAOCAI , XIAO YUE , LI CHENG 
Published: October 2022

Based on the microdata of Chinese listed enterprises from 2012 to 2017, we empirically examine the nonlinear relationship between institutional ownership and enterprise innovation. We find that institutional ownership has an inverted-U nonlinear relationship with enterprise patenting when enterprise characteristics and fixed effects such as time, region, industry type and ownership type of enterprises (SOE or NSOE) are controlled and the endogeneity is considered. This nonlinear relationship significantly varies among active, passive, pressure-resistant and pressure-sensitive groupings of institutional investors. Employing the mediation model proposed by Hayes and Preacher (2010) [Quantifying and testing indirect effects in simple mediation models when the constituent paths are nonlinear. Multivariate Behavioral Research, 45(4), 627–660], we further investigate the mediating effects of financing constraints and R&D manipulation. The results show that institutional ownership linearly drives enterprise innovation by alleviating financing constraints but nonlinearly affects the enterprise innovation by manipulating R&D activities.
Ordovician biostratigraphy: index fossils, biozones and correlation
Authors: Goldman Daniel , Leslie Stephen A. , Liang Yan , Bergström Stig M. 
Published: October 2022

Abstract
Two remarkable events in the history of life on the Earth occur during the Ordovician Period (486.9–443.1 Ma). The first is an exceptionally rapid and sustained radiation of marine life known as the ‘Great Ordovician Biodiversification Event’ (GOBE), and the second is a catastrophic Late Ordovician mass extinction (LOME). Understanding the duration, rate and magnitude of these events requires an increasingly precise global correlation framework. In this chapter we review the major subdivisions of the Ordovician System, their Global Stratotype Section and Points, and the chronostratigraphic levels that define their bases. We also present a detailed set of correlation charts that illustrate the relationships between most of the regional graptolite, conodont and chitinozoan successions across the world.
Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer
Authors: Vaishampayan Ulka N. , Thakur Archana , Chen Wei , Deol Abhinav , Patel Meera , Dobson Kimberlee , Dickow Brenda , Schalk Dana , Schienschang Amy , Whitaker Sarah , Polend Amanda , Fontana Joseph A. , Heath Elisabeth I. , Lum Lawrence G. 
Published: October 2022

Abstract

Purpose:
A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 bispecific antibody (HER2Bi)-armed activated T cells (HER2 BAT) and programmed death 1 inhibitor, pembrolizumab.

Patients and Methods:
Patients with metastatic castration-resistant prostate cancer (mCRPC) with 0 to 1 performance status and normal liver, kidney, and marrow function, pre- or post-docetaxel chemotherapy were eligible. Primary endpoint was 6-month progression-free survival (PFS). Peripheral blood mononuclear cells were obtained by a single apheresis, shipped to University of Virginia, activated with OKT3 and expanded for 14 days in IL2, harvested, and armed with HER2Bi and cryopreserved. HER2 BATs were infused twice weekly for 4 weeks and pembrolizumab was administered every 21 days for a maximum duration of 6 months starting 1 to 3 weeks prior to HER2 BATs infusion.

Results:
Fourteen patients were enrolled with a median age of 69 (range 57–82 years) and median PSA of 143.4 (range 8.2–4210 ng/dL). Two patients had peritoneal metastases, 1 had lymph node (LN) only metastases and 11 had bone metastases of which 7 had bone and LN metastases. All were pretreated with androgen receptor axis targeted agents and 7 (50%) had prior docetaxel chemotherapy. The toxicities were grade1–2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month PFS was achieved in 5 of 14 patients (38.5%; 95% confidence interval, 19.5%–76.5%). Median PFS was 5 months and median survival was 31.6 months.

Conclusions:
The safety and promising efficacy makes this combination worthy of future investigation in mCRPC.
Sarcopenic Obesity Is Associated With Reduced Cardiorespiratory Fitness Compared With Nonsarcopenic Obesity in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Billingsley Hayley E. , Del Buono Marco Giuseppe , Canada Justin M. , Kim Youngdeok , Damonte Juan Ignacio , Trankle Cory R. , Halasz Geza , Mihalick Virginia , Vecchié Alessandra , Markley Roshanak R. , Kadariya Dinesh , Bressi Edoardo , Medina de Chazal Horacio , Chiabrando Juan Guido , Mbualungu James , Turlington Jeremy , Arena Ross , Van Tassell Benjamin W. , Abbate Antonio , Carbone Salvatore 
Published: October 2022

Background:
Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF.

Methods:

Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO
2
), circulatory power, oxygen uptake efficiency slope, O
2
pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate.

Results:

Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO
2
(NSO, 1.62±0.53 L·min
-1
versus SO, 1.27±0.44 L·min
-1
,
P
=0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48,
P
=0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds,
P
=0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO
2
when adjusted for age, sex, adiposity, and HF severity.

Conclusions:
In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.