bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of rifampicin on the pharmacokinetics and safety of carotegrast methyl in healthy subjects: A randomized 2 × 2 crossover study
Authors: Imai Hiromitsu , Oikawa Ichiro , Koyama Tetsuya , Matsuki Shunji 
Published: February 2024

AbstractAimsTo evaluate the effect of the combination of carotegrast methyl with rifampicin, a potent inhibitor of organic anion transporter polypeptide, on the pharmacokinetics (PKs), safety and tolerability of carotegrast methyl.MethodsIn this 2 × 2 crossover study in 20 healthy Japanese adults, 10 subjects received carotegrast methyl 960 mg and rifampicin 600 mg on day 1 and received carotegrast methyl 960 mg on day 8. The subjects in the other sequence received the same treatments but in the opposite order. The 90% confidence interval (CI) of the geometric mean ratio of the Cmax and AUC0‐t for carotegrast, the main active metabolite of carotegrast methyl, with/without rifampicin was calculated. If the 90% CI fell within the range of 0.80‐1.25, this indicated the absence of any drug‐drug interaction. Adverse events (AEs) were monitored.ResultsThe geometric mean ratios (90% CI) of the Cmax and AUC0‐t for carotegrast with/without rifampicin were 4.78 (3.64‐6.29) and 5.59 (4.60‐6.79), respectively, indicating that carotegrast has a PK interaction with rifampicin. The combination with rifampicin increased the exposure of carotegrast and also that of its metabolites. The incidence of any AEs with/without rifampicin was five (25.0%) and one (5.0%), respectively.ConclusionsCoadministration of carotegrast methyl with rifampicin significantly increased the exposure of carotegrast compared with carotegrast methyl administration alone. In this single dose study, the incidence of AEs of carotegrast methyl with rifampicin increased compared with carotegrast methyl alone, but the incidence of adverse drug reactions did not increase with combination administration.
In search of respect and continuity of care: Hungarian women's experiences with midwifery‐led, community birth
Authors: Rubashkin Nicholas , Bingham Brianna , Baji Petra , Szebik Imre , Kremmer Sarolta , Vedam Saraswathi 
Published: February 2024

AbstractIntroductionTo describe and compare intervention rates and experiences of respectful care when Hungarian women opt to give birth in the community.MethodsWe conducted a cross‐sectional online survey (N = 1257) in 2014. We calculated descriptive statistics comparing obstetric procedure rates, respectful care indicators, and autonomy (MADM scale) across four models of care (public insurance; chosen doctor or chosen midwife in the public system; private midwife‐led community birth). We used an intention‐to‐treat approach. After adjusting for social and clinical covariates, we used logistic regression to estimate the odds of obstetric procedures and disrespectful care and linear regression to estimate the level of autonomy (MADM scale).FindingsIn the sample, 99 (7.8%) saw a community midwife for prenatal care. Those who planned community births had the lowest rates of cesarean at 9.1% (public: 30.4%; chosen doctor: 45.2%; chosen midwife 16.5%), induced labor at 7.1% (public: 23.1%; chosen doctor: 26.0%; chosen midwife: 19.4%), and episiotomy at 4.44% (public: 62.3%; chosen doctor: 66.2%; chosen midwife: 44.9%). Community birth clients reported the lowest rates of disrespectful care at 25.5% (public: 64.3%; chosen doctor: 44.3%; chosen midwife: 38.7%) and the highest average MADM score at 31.5 (public: 21.2; chosen doctor: 25.5; chosen midwife: 28.6). In regression analysis, community midwifery clients had significantly reduced odds of cesarean (0.35, 95% CI 0.16–0.79), induced labor (0.27, 95% CI 0.11–0.67), episiotomy (0.04, 95% CI 0.01–0.12), and disrespectful care (0.36, 95% CI 0.21–0.61), while also having significantly higher average MADM scores (5.71, 95% CI 4.08–7.36).ConclusionsHungarian women who plan to give birth in the community have low obstetric procedure rates and report greater respect, in line with international data on the effects of place of birth and model of care on experiences of perinatal care.
Paraproteinemia‐associated neuropathy with or without anti‐myelin‐associated glycoprotein antibody
Authors: Nakajima Masanori 
Published: February 2024

AbstractParaproteinemia‐associated neuropathy (PAN) develops with paraproteinemia and is mainly caused by the monoclonal proliferation of mature B cells, especially monoclonal gammopathy of undetermined significance (MGUS). PAN tends to increase with age, and in a super‐aging society, its frequency is expected to increase. Among paraproteinemias, the immunoglobulin (Ig)G type is most common, but the frequency of PAN is reported to be higher for the IgM type. IgG/IgA‐type PAN includes MGUS, plasma cell myeloma, and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome. IgM‐type PAN includes anti‐myelin‐associated glycoprotein antibody‐associated neuropathy, chronic ataxic neuropathy with IgM antibody that recognizes disialosyl ganglioside and IgM‐type PAN without anti‐nerve antibodies. Light chain‐type PAN includes immunoglobulin‐related amyloidosis. PAN has the characteristics of a blood disease, as well as an immune‐mediated disease, and is treated by immunotherapy. As an example, anti‐myelin‐associated glycoprotein antibody‐associated neuropathy is treated with rituximab, plasmapheresis and intravenous immunoglobulin therapy, but their effectiveness has not been established. As novel treatments, lenalidomide, Bruton tyrosine kinase inhibitors, B‐cell lymphoma 2 inhibitors and mimetic human natural killer‐1 epitope polymers have been investigated. By analyzing the human natural killer‐1‐related sugar chain structure as an antigen, the selective removal of pathological antibodies might be a new therapeutic target.
Increases in the use of drug testing kits among nightclub and festival attendees in New York City who use ecstasy, 2017–2022
Authors: Fitzgerald Nicole D. , Palamar Joseph J. 
Published: February 2024

AbstractIntroductionEcstasy (3,4‐methylenedioxymethamphetamine [MDMA]) is a drug commonly used by people who attend electronic dance music (EDM) events at nightclubs and dance festivals. Drug checking has gained popularity in recent years to test for adulterants, but epidemiology studies are needed to estimate potential shifts in prevalence of drug checking to further inform harm reduction efforts.MethodsAdults entering randomly selected EDM events in New York City were surveyed in 2017 and 2022. Those reporting past‐year ecstasy use were asked if they tested their ecstasy in the past year using a drug testing kit and whether they found out or suspected their ecstasy contained other drugs. We compared estimates between 2017 and 2022.ResultsIn 2017, an estimated 23.1% had tested their ecstasy, and this estimate increased to 43.1% in 2022 (86.6% increase, p = 0.006). Among those who tested their ecstasy, in 2017, 31.2% always tested their drug, and this increased to 60.6% in 2022 (94.2% increase, p = 0.026). In 2017, 59.6% of those who tested their ecstasy reported finding out or suspecting their drug was adulterated, which decreased to 18.4% in 2022 (69.1% decrease, p < 0.001). Suspected methamphetamine adulteration in particular decreased, from 21.9% in 2017 to 3.6% in 2022 (83.6% decrease, p = 0.007).Discussion and ConclusionsThe use of drug testing kits has increased among EDM event attendees who use ecstasy and, at the same time, among those who had tested their ecstasy, suspected adulteration has decreased. Continued interest in understanding ecstasy contents among this population suggests the need for formal drug checking services.
Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial
Authors: Mujanovic Adnan , Dobrocky Tomas , Pfeilschifter Waltraud , Remonda Luca , Caroff Jildaz , Behme Daniel , Seiffge David J. , Cereda Carlo W. , Kägi Georg , Leyon Joe , Piechowiak Eike I. , Costalat Vincent , Wagner Judith , Chabert Emmanuel , Meinel Thomas R. , Jansen Olav , Alonso Angelika , Loehr Christian , Liebeskind David S. , Gralla Jan , Fischer Urs , Kaesmacher Johannes ,   the SWIFT DIRECT investigators
Published: February 2024

AbstractBackground and purposeThe value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT‐only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting.MethodsSWIFT DIRECT randomized IVT‐eligible patients to either EVT + IVT or EVT‐only. Primary outcome was 90‐day functional independence (modified Rankin Scale score 0–2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90‐day all‐cause mortality. Interaction models were fitted for all predefined outcomes.ResultsAmong 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non‐tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non‐tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05).ConclusionsNo treatment effect heterogeneity of EVT + IVT versus EVT‐only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.
ITAM‐based receptors in natural killer cells
Authors: Aguilar Oscar A. , Fong Lam‐Kiu , Lanier Lewis L. 
Published: February 2024

SummaryThe ability of cells of the immune system to acquire features such as increased longevity and enhanced secondary responses was long thought to be restricted to cells of the adaptive immune system. Natural killer (NK) cells have challenged this notion by demonstrating that they can also gain adaptive features. This has been observed in both humans and mice during infection with cytomegalovirus (CMV). The generation of adaptive NK cells requires antigen‐specific recognition of virally infected cells through stimulatory NK receptors. These receptors lack the ability to signal on their own and rather rely on adaptor molecules that contain ITAMs for driving signals. Here, we highlight our understanding of how these receptors influence the production of adaptive NK cells and propose areas in the field that merit further investigation.
Leaving no one behind: Why social protection must include displaced people
Authors: Polvanesi Mattia 
Published: February 2024

AbstractUNHCR, the UN Refugee Agency, has the mandate to save lives and build better futures for millions of forcibly displaced and stateless people. This contribution sets out UNHCR’s mandated roles concerning displaced population groups and details the nature of the humanitarian and human development challenges that confront the international community. In this important regard, the social protection coverage extension objectives of the 2030 Agenda for Sustainable Development and the Global Partnership for Universal Social Protection (USP), to leave no one behind, are considered essential.
Insourcing versus outsourcing in a vertical structure
Authors: Shin Dongsoo , Strausz Roland 
Published: February 2024

AbstractWe study an agency model with vertical hierarchy—the principal, the prime‐agent and the subagent. The principal faces a project that needs both agents' services. Due to costly communication, the principal receives a report only from the prime‐agent, who receives a report from the subagent. The principal can directly incentivize each agent by setting individual transfers (insourcing), or sets only one overall transfer to an independent organization in which the prime‐agent hires the subagent (outsourcing). We show that insourcing is always optimal when the principal can perfectly process the prime‐agent's report. When the principal's information process is limited, however, outsourcing can be the prevailing mode of operation. In addition, insourcing under limited information process is prone to collusion between the agents, whereas no possibility of collusion arises with outsourcing.
A scoping review of parenteral requirements (macronutrients, fluid, electrolytes and micronutrients) in adults with chronic intestinal failure receiving home parenteral nutrition
Authors: Baker Melanie , French Chloe , Hann Mark , Lal Simon , Burden Sorrel 
Published: February 2024

AbstractIntroductionHome parenteral nutrition (HPN) prescriptions should be individualised in adults with chronic intestinal failure (IF). The aims of the review were to explore HPN requirements and available guidelines and to determine whether adults (≥ 18 years) receive recommended parenteral nutrient doses.MethodsOnline databases searches identified empirical evidence (excluding case‐reports), reviews and guidelines (Published 2006–2024 in English language). Additional reference lists were hand‐searched. Older studies, cited in national guidelines were highlighted to map evidence source. Two reviewers screened 1660 articles independently, with 98 full articles assessed and 78 articles included (of which 35 were clinical studies). Citation tracking identified 12 older studies.ResultsA lack of evidence was found assessing parenteral macronutrient (amounts and ratios to meet energy needs), fluid and electrolyte requirements. For micronutrients, 20 case series reported serum levels as biomarkers of adequacy (36 individual micronutrient levels reported). Studies reported levels below (27 out of 33) and above (24 out of 26) reference ranges for single micronutrients, with associated factors explored in 11 studies. Guidelines stated recommended parenteral dosages. Twenty‐four studies reported variable proportions of participants receiving HPN dosages outside of guideline recommendations. When associated factors were assessed, two studies showed nutrient variation with type of HPN administered (multichamber or individually compounded bags). Five studies considered pathophysiological IF classification, with patients with short bowel more likely to require individualised HPN and more fluid and sodium.ConclusionsThis review highlights substantial evidence gaps in our understanding of the parenteral nutritional requirements of adult receiving HPN. The conclusions drawn were limited by temporal bias, small samples sizes, and poor reporting of confounders and dose. Optimal HPN nutrient dose still need to be determined to aid clinical decision‐making and further research should explore characteristics influencing HPN prescribing to refine dosing recommendations.
Structural insights into the Oryza sativa cation transporters HKTs in salt tolerance
Authors: Gao Ran , Jia Yutian , Xu Xia , Fu Peng , Zhou Jiaqi , Yang Guanghui 
Published: February 2024

ABSTRACTThe high‐affinity potassium transporters (HKTs), selectively permeable to either Na+ alone or Na+/K+, play pivotal roles in maintaining plant Na+/K+ homeostasis. Although their involvement in salt tolerance is widely reported, the molecular underpinnings of Oryza sativa HKTs remain elusive. In this study, we elucidate the structures of OsHKT1;1 and OsHKT2;1, representing two distinct classes of rice HKTs. The dimeric assembled OsHKTs can be structurally divided into four domains. At the dimer interface, a half‐helix or a loop in the third domain is coordinated by the C‐terminal region of the opposite subunit. Additionally, we present the structures of OsHKT1;5 salt‐tolerant and salt‐sensitive variants, a key quantitative trait locus associated with salt tolerance. The salt‐tolerant variant of OsHKT1;5 exhibits enhanced Na+ transport capability and displays a more flexible conformation. These findings shed light on the molecular basis of rice HKTs and provide insights into their role in salt tolerance.
Impact of knowledge, attitudes and self‐reported practices of nurses on early mobilization of mechanically ventilated patients in the ICU
Authors: Sui Weijing , Gong Xiaoyan , Zhuang Yiyu 
Published: February 2024

AbstractBackgroundMany ICUs worldwide are striving to integrate early mobilization as part of critical care rehabilitation. However, ICU nurses, who are essential contributors to the early mobilization of critically ill patients, still lack comprehensive surveys assessing their knowledge, beliefs, and practices regarding the early mobilization of mechanically ventilated patients.AimTo analyse the knowledge, attitudes, and practices of intensive care unit (ICU) nurses regarding the early mobilization of mechanically ventilated patients and to explore the effects of these practices.Study DesignA multicentre cross‐sectional study. ICU nurses in five tertiary hospitals in Zhejiang Province, China, were selected by convenience sampling and invited to complete an online questionnaire between 1 June 2021 and 15 June 2021. Sociodemographic data and the knowledge, attitudes, and practices of ICU nurses regarding early mobilization.ResultsA total of 296 valid questionnaires were collected, for a response rate of approximately 77.5%. The average scores for knowledge, attitudes, and practices of ICU nurses regarding the early mobilization of mechanically ventilated patients were 42.7 ± 7.4, 34.3 ± 6.5, and 47.1 ± 6.5, respectively, which were good scores. Quantile regressions showed that at the 25% and 50% quartiles, increases in knowledge and attitude scores resulted in increases in practice scores (p < .001); however, at the 75% quartile, increases in knowledge scores did not result in practice score increases (t = 0.000, p = .999); moreover, there was still a 0.5‐point increase in practice scores per 1‐point increase in attitude scores (t = 0.500, p < .001).ConclusionsThe knowledge, attitudes, and self‐reported practices of ICU nurses were good, although there is room for improvement. Considering that the influence of attitudes on practice improvement is more important than knowledge, ICU managers should promote knowledge transformation, strengthen attitudes, and adopt comprehensive measures to promote the early mobilization of mechanically ventilated patients in the ICU.Relevance to Clinical PracticeTo optimize the early mobilization of mechanically ventilated patients in the ICU, introducing multipronged support strategies based on the knowledge and attitudes of ICU nurses is recommended to promote the implementation of such practices.
Functional treatment of bilateral posterior crossbite improves mandibular kinematics during chewing
Authors: Piancino Maria Grazia , Vallelonga Teresa , De Biase Corrado , Di Benedetto Laura , Crincoli Vito , Tortarolo Alessandro 
Published: February 2024

AbstractObjectivesTo evaluate the effects of treatment of bilateral posterior crossbite (BPXB) on mandibular kinematics by the percentage of reverse chewing cycles (RCCs) during soft and hard bolus chewing before and after the correction of the malocclusion with function‐generating bite (FGB).Materials and MethodsThis prospective study included 71 subjects: 19 patients with occlusally symmetric BPXB (M = 9; F = 10; mean age 9.3 ± 2.2[yr.mo]), 32 patients with occlusally asymmetric BPXB (19 with more teeth in crossbite on the right side (right prevalent side), M = 7; F = 12; mean age 8.2 ± 1.6 [yr.mo] and 13 on the left side, M = 7; F = 6; mean age 9.6 ± 1.9 [yr.mo]) and 20 controls without malocclusion (M = 8; F = 12; mean age 10.2 ± 1.7 [yr.mo]). Masticatory patterns were recorded before (T0) and after (T1) the correction of the malocclusion with FGB, with the K7‐I® kinesiograph using standardized soft and hard boluses.ResultsBPXB was corrected in all included patients. At T0, the percentage of RCCs in BPXB was significantly increased compared to controls (P < .0001); symmetric BPXB showed no difference in RCCs between the sides, whereas asymmetric BPXB showed significantly more RCCs on the side with more teeth in crossbite (prevalent side). After treatment with FGB (T1), the percentage of RCCs was significantly reduced in both symmetric BPXB patients (soft bolus, P = .003; hard bolus, P < .001) and asymmetric BPXB patients (prevalent side: soft and hard bolus, P < .00001; non‐prevalent side: soft bolus, P = .01 and hard bolus, P = .0002).ConclusionFunctional correction of BPXB with FGB significantly improved mandibular kinematics during chewing.
JMJD2A mediates transcriptional activation of SFRP4 and regulates oxidative stress and mitochondrial dysfunction in heart failure
Authors: Ren Mingming , Ye Xiaoqiang , Ouyang Chun , Da Qing'en , Xue Weiwei , Chen Piji 
Published: February 2024

AbstractThe importance of mitochondrial dysfunction and oxidative stress has been indicated in the progression of heart failure (HF). The molecular mechanisms, however, remain to be fully elucidated. This study aimed to explore the role and underlying mechanism of secreted frizzled‐related protein 4 (SFRP4) in these two events in HF. Mice with HF were developed using transverse aortic constriction, and hematoxylin‐eosin staining, MASSON staining, and Terminal deoxynucleotidyl transferase (TdT)‐mediated 2'‐Deoxyuridine 5'‐ Triphosphate nick end labeling (TUNEL assays) were conducted to detect morphological damage in the myocardial tissues of mice. HL‐1 mouse cardiomyocytes were induced with isoproterenol (ISO), and cell viability and apoptosis were examined using cell counting kit‐8 and TUNEL assays. SFRP4 and Jumonji domain‐containing protein 2A (JMJD2A) were highly expressed in myocardial tissues. Suppression of SFRP4 alleviated apoptosis and fibrosis in myocardial tissues of mice. In addition, the extent of mitochondrial dysfunction and oxidative stress in damaged myocardial tissues and HL‐1 cells was mitigated by SFRP4 inhibition as well. JMJD2A catalyzed demethylation modification of the SFRP4 promoter, thus promoting SFRP4 transcription in the development of HF. JMJD2A is responsible for SFRP4 transcription activation in the failing hearts of mice. Blockade of JMJD2A or SFRP4 might be a novel therapy effective in mitigating HF progression.
Carcinogenesis caused by transcription‐coupled DNA damage through GANP and other components of the TREX‐2 complex
Authors: Sakai Yasuhiro , Kuwahara Kazuhiko 
Published: February 2024

AbstractPerturbation of genes is important for somatic hypermutation to increase antibody affinity during B‐cell immunity; however, it may also promote carcinogenesis. Previous studies have revealed that transcription is an important process that can induce DNA damage and genomic instability. Transciption‐export‐2 (TREX‐2) complex, which regulates messenger RNA (mRNA) nuclear export, has been studied in the budding yeast Saccharomyces cerevisiae; however, recent studies have started investigating the molecular function of the mammalian TREX‐2 complex. The central molecule in the TREX‐2 complex, that is, germinal center‐associated nuclear protein (GANP), is closely associated with antibody affinity maturation as well as cancer etiology. In this review, we focus on carcinogenesis, lymphomagenesis, and teratomagenesis caused by transcription‐coupled DNA damage through GANP and other components of the TREX‐2 complex. We review the basic machinery of mRNA nuclear export and transcription‐coupled DNA damage. We then briefly describe the immunological relationship between GANP and the affinity maturation of antibodies. Finally, we illustrate that the aberrant expression of the components of the TREX‐2 complex, especially GANP, is associated with the etiology of various solid tumors, lymphomas, and testicular teratoma. These components serve as reliable predictors of cancer prognosis and response to chemotherapy.