bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol of a drug–drug interaction study between bictegravir/emtricitabine/tenofovir alafenamide and feminizing hormones in trans women living with HIV
Authors: Lacombe‐Duncan Ashley , Tseng Alice , Scarsi Kimberly K. , Senneker Tessa , Kluger Hadas , Persad Yasmeen , Underhill Angela , Kennedy V. Logan , Armstrong Ian , Fung Raymond , Bourns Amy , Nguyen Quang , Hranilovic Susan , Weisdorf Thea , Chan Louie , Kia Hannah , Halpenny Roberta , Iyer Harshita , Jeyarajah Nirubini , Kovchazov George , Tharao Wangari , Loutfy Mona 
Published: July 2024

AimsTrans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug–drug interactions (DDIs) between ART drugs and gender‐affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen‐suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)].MethodsWe present a protocol for a three‐armed, parallel‐group, longitudinal (6‐month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily oral oestradiol and an anti‐androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2.DiscussionThis study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life‐saving therapies for trans women with HIV.
Estimation of self‐funded human papillomavirus vaccine recipients from Japan's previously assumed “unvaccinated generation”
Authors: Kobayashi Mariya , Nakagawa Satoshi , Ueda Yutaka , Yagi Asami , Kakuda Mamoru , Hiramatsu Kosuke , Kimura Tadashi 
Published: July 2024

AbstractPrecise vaccination data is essential to accurately estimate the effectiveness of the human papillomavirus (HPV) vaccine against HPV‐related cancers. In Japan, the number of subsidized HPV vaccinations can be tracked through registries, but the number of self‐funded vaccinations has not been tracked. The number of individuals who chose to receive the vaccine at their own expense, despite being ineligible for public subsidies due to their age, is unknown and has been nominally considered to be zero. Our aim is to produce a more accurate estimate of this number using recently released proprietary data. First, we estimated the total number of self‐funded HPV vaccinations occurring from 2010 to 2012 using public data from the Ministry of Health, Labour and Welfare and our previously reported data on the number of HPV vaccinations eligible for public subsidy. Second, using proprietary data from the vaccine manufacturer, we calculated the distribution of self‐funded vaccination shots by age. Finally, we combined these data to estimate the number of self‐funded HPV vaccinations by birth fiscal year (FY) relative to a yearly reference population. We found that 78,264 individuals born in FY1993 and 58,190 born in FY1992 self‐funded their vaccinations, representing 13.6% and 10.0% of the reference population, respectively. Additionally, we found that 5%–10% of individuals born from FY1986 to FY1991 self‐funded their vaccinations. Our study revealed for the first time that a certain number of individuals from the “HPV unvaccinated generation,” ineligible for subsidies due to age restrictions, chose to self‐fund their vaccinations.
‘There was nothing, just absolute darkness’: Understanding the needs of those caring for children and young people with complex neurodisability in a diverse UK context: A qualitative exploration in the ENCOMPASS study
Authors: Prest Kirsten , Wilson Emma , Vassiliadou Io , Ali Sayeeda , Lakhanpaul Monica , Morris Christopher , Tann Cally , Harniess Phillip , Lewis‐Jackson Sasha , Kuper Hannah , Heys Michelle 
Published: July 2024

AbstractBackgroundChildren and young people (CYP) with complex neurodisability experience multiple physical, communication, educational and social challenges, which require complex packages of multidisciplinary care. Part of the holistic care required includes supporting the families and parents/caregivers. The aim of the wider study was to introduce a new programme (‘Ubuntu’) to parents/caregivers and healthcare professionals (HCPs) in order to test the feasibility and acceptability of the concept and content, with the goal of potential adaptation for the UK in mind. Data collection and analysis uncovered rich data on caregiving journeys, navigation of health services, and perceived service gaps. This paper focuses solely on these topics. Further papers will report on the feasibility and adaptation data.MethodsTwo rounds of semi‐structured interviews were conducted with 12 caregivers of CYP with complex neurodisability and six HCPs from a variety of disciplines, recruited from a community child health service in London Borough of Newham, UK in 2020. The interviews included open‐ended questions to explore caregiving journeys, experiences of navigating health services and perceived service gaps. Transcripts were analysed using a data‐driven inductive thematic analysis.ResultsThree themes were identified that related to the aim of understanding caregivers' experiences and unmet needs relating to current service provision. These were (1) Caregiver Mental Health, (2) The Information Gap and (3) The Need for Holistic Support. Mental health difficulties were reported, particularly around the period of diagnosis. Priority needs included the provision of clear information about the diagnosis and services offered, opportunities to forge peer support networks and for services across the community to collaborate.ConclusionsThe delivery of health services for CYP with neurodisability should encompass the broad needs of the family as well as meeting the clinical needs of the CYP.
Monitoring levetiracetam concentration in saliva during pregnancy is stable and feasible
Authors: Li Wanling , Yang Ximeng , Chen Qian , Wang Zhenlei , Duan Yifei , Chen Lei 
Published: July 2024

AbstractAimsThis multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy.MethodsThe slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC–MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose‐normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy.ResultsIn total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 μg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915–0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 μg/mL (upper limit) with an AUC of 0.952 (0.914–0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007.ConclusionThe saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non‐pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.
Activation of GPER1 by G1 prevents PTSD‐like behaviors in mice: Illustrating the mechanisms from BDNF/TrkB to mitochondria and synaptic connection
Authors: Chen Lixia , Zhang Yang , Wang Zisheng , Zhang Zhengrong , Wang Jingji , Zhu Guoqi , Yang Shaojie 
Published: July 2024

AbstractBackgroundG1 is a specific agonist of G protein‐coupled estrogen receptor 1 (GPER1), which binds and activates GPER1 to exert various neurological functions. However, the preventive effect of G1 on post‐traumatic stress disorder (PTSD) and its mechanisms are unclear.ObjectiveTo evaluate the protective effect of G1 against synaptic and mitochondrial impairments and to investigate the mechanism of G1 to improve PTSD from brain‐derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling.MethodsThis study initially detected GPER1 expression in the hippocampus of single prolonged stress (SPS) mice, utilizing both Western blot and immunofluorescence staining. Subsequently, the effects of G1 on PTSD‐like behaviors, synaptic, and mitochondrial functions in SPS mice were investigated. Additionally, the involvement of BDNF/TrkB signaling involved in the protection was further confirmed using GPER1 antagonist and TrkB inhibitor, respectively.ResultsThe expression of GPER1 was reduced in the hippocampus of SPS mice, and G1 treatment given for 14 consecutive days significantly improved PTSD‐like behaviors in SPS mice compared with model group. Electrophysiological local field potential (LFP) results showed that G1 administration for 14 consecutive days could reverse the abnormal changes in the gamma oscillation in the CA1 region of SPS mice. Meanwhile, G1 administration for 14 consecutive days could significantly improve the abnormal expression of synaptic proteins, increase the expression of mitochondria‐related proteins, increase the number of synapses in the hippocampus, and ameliorate the damage of hippocampal mitochondrial structure in SPS mice. In addition, G15 (GPER1 inhibitor) and ANA‐12 (TrkB inhibitor) blocked the ameliorative effects of G1 on PTSD‐like behaviors and aberrant expression of hippocampal synaptic and mitochondrial proteins in SPS mice and inhibited the reparative effects of G1 on structural damage to hippocampal mitochondria, respectively.ConclusionG1 improved PTSD‐like behaviors in SPS mice, possibly by increasing hippocampal GPER1 expression and promoting BDNF/TrkB signaling to repair synaptic and mitochondrial functional impairments. This study would provide critical mechanism for the prevention and treatment of PTSD.
Efficacy and Safety of Azvudine in Patients With COVID‐19 in China: A Meta‐Analysis of Observational Studies
Authors: Dong Tao , Zhang Wentao , Wu Tingting , Ge Yongxiang , Yang Qi , Xu Jia , Liu Yuna 
Published: July 2024

ABSTRACTBackgroundAzvudine (FNC) is a novel small molecule antiviral drug for treating COVID‐19 that is available only on the Chinese market. Despite being recommended for treating COVID‐19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID‐19 outcomes and its safety.MethodsWe followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID‐19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T‐FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS‐I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence.ResultsThe meta‐analysis included 24 retrospective studies involving a total of 11 830 patients. Low‐certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76–1.08) or LOHS (WMD = −0.24, 95% CI: −0.83 to 0.35) between FNC and Paxlovid in COVID‐19 patients. Low‐certainty evidence shows that the T‐FNANC was longer (WMD = 1.95, 95% CI: 0.36–3.53). Compared with the Paxlovid group, low‐certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63–0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46–0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID‐19 patients (OR = 0.61, 95% CI: 0.51–0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50–0.91), and very low certainty evidence shows significantly decreased the T‐FNANC (WMD = −4.62, 95% CI: −8.08 to −1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = −0.70, 95% CI: −3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48–8.17).ConclusionsFNC appears to be a safe and potentially effective treatment for COVID‐19 in China, but further research with larger, high‐quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are applicable worldwide.Trial RegistrationPROSPERO number: CRD42024520565
Placental Transmogrification of the Lung Presenting as Cystic‐Solid Mass: A Case Report
Authors: Liu Chen , Zhang Yunhui , Li Dengyuan , Sun Danxiong 
Published: July 2024

ABSTRACTThe gradually progressive solitary cystic‐solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29‐year‐old woman with a persistent cystic‐solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic‐solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.
Myelodysplasia cutis and VEXAS syndrome initially diagnosed as histiocytoid Sweet syndrome: A diagnostic pitfall
Authors: Shimshak Serena J. , Jasmine Sion , Davis Mark D. P. , Johnson Emma F. , Peters Margot S. , Zheng Gang , Sokumbi Olayemi , Comfere Nneka I. 
Published: July 2024

AbstractHistiocytoid Sweet syndrome (H‐SS) is a histopathological variant of Sweet syndrome (SS) defined by cutaneous infiltration of immature myeloid cells morphologically resembling histiocytes. The association of H‐SS with underlying malignancy, particularly myelodysplastic syndromes, is well‐established. Myelodysplasia cutis (MDS‐cutis) has been proposed to describe cases historically diagnosed as H‐SS but characterized by shared clonality of the myeloid infiltrate in skin and bone marrow. Therefore, identifying patients who might have MDS‐cutis is critical for the management of the associated hematologic malignancy. VEXAS syndrome, an adult‐onset autoinflammatory disease, should also be included in the histopathologic differential diagnosis of H‐SS, as it shares clinical and pathologic features with MDS‐cutis. Through the presentation of two cases, we aim to highlight the defining features and key clinical implications of MDS‐cutis and VEXAS syndrome.
A cross‐sectional time series of cardiometabolic health education format preferences across sociodemographic groups
Authors: Woolley Angharad , Hadjiconstantinou Michelle , Bodicoat Danielle H. , Khunti Kamlesh , Davies Melanie J. , Seidu Samuel 
Published: July 2024

AbstractAimsHealth education is integral to cardiometabolic disease (CMD) management. This study aimed to assess whether and how education preferences have changed over time, and whether trends differ by sociodemographic characteristics (education status, age, ethnicity, and sex).MethodsA cross‐sectional questionnaire was deployed across five counties in the East Midlands, UK between 2017 and 2022 to adults with CMD (type 2 diabetes, cardiovascular disease or cerebrovascular disease). Respondent demographic data were collected alongside health education preferences. Statistical analyses ascertained whether demographic characteristics influenced preferences. The distribution of preferences over time was charted to identify trends.ResultsA total of 4301 eligible responses were collected. Face‐to‐face one‐to‐one education was preferred (first choice for 75.1% of participants) but popularity waned over the five‐year period. Trends were similar amongst demographic groups. Online education showed a U‐shaped trend: In 2017, 44% of respondents ranked it as acceptable, peaking at 53% in 2019, but declining again, to below base line, 43%, by 2022. This modality was more popular with participants aged younger than 65 years, but popularity in people older than 65 years increased over the study period. The popularity of printed information also declined over time across all demographic groups except those of South Asian ethnicity, for whom it remained static.ConclusionsThe overwhelming preference for face‐to‐face one‐to‐one health education from a doctor or nurse highlights the importance of preserving access to this modality, even in the face of current NHS pressures and trends towards digitalisation. Trends are changing, and should continue to be monitored, including between different sociodemographic groups.
Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase
Authors: Ghidoni Céline , van der Stouwe Jan Gerrit , Würzburger Laura , Wiech Patrick , Vontobel Jan , Bohm Philipp , Moser Georg , Petrasch Gloria , Rossi Valentina A. , Schmied Christian M. , Caselli Stefano , Niederseer David 
Published: July 2024

AbstractBackgroundHypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE.Methods800 patients aged 17–90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre‐existent hypertension.ResultsOf the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (β [95% CI] 8.0 [4.9–11.1]) and diastolic (2.4 [0.4–4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2–9.4]) and diastolic BP (4.5 [1.9–7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1–7.5]) and fully adjusted (5.5 [1.1–10.0]) models. There was no difference in maximum diastolic BP between groups.ConclusionIn this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.
Control and management ofPhytophthoradamage in forestry—A systematic mapping study
Authors: López‐García Noelia , Romeralo Carmen , Rönnberg Jonas , Witzell Johanna 
Published: July 2024

AbstractPlant pathogens in the genusPhytophthoraare a severe threat to forest plantations, ecosystems and tree nurseries. Especially in forests and natural ecosystems, there is a lack of effective measures to control and manage these pathogens. In this study, we conducted a systematic mapping review to collate evidence regarding the control and management of forestPhytophthorain different production settings and ecosystems. The study aimed to reveal possible knowledge gaps, thus guiding future research priorities. We extracted information from nine databases, limiting the search to studies published during the time period from January 2010 to December 2022. The articles were shared between three reviewers who classified the reports using a set of inclusion/exclusion criteria. A total of 561 articles were included and mapped in a database using pre‐defined coding, and critically appraised for relevance and reliability. The analysis showed that biological or bio‐based measures were the most studied interventions, followed by genetics or breeding programmes, whereas chemical and silvicultural management approaches were less studied. Most of the studies were conducted in Europe, North America, Australia and New Zealand.Phytophthora cinnamomihas been the most studied species followed byP. ramorum. We discuss the current knowledge gaps in the implementation of existing research, likely due to a lack of holistic understanding of the processes over time and space, and suggest future research that is needed to managePhytophthorain forest ecosystems.
Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species‐activated P38 MAPK signal pathway
Authors: Feng Yu‐Heng , Tang Ren‐Jie , Zhang Yan‐Yan , Lin Jiu , Liu Ya‐Jing , Li Yi‐Ke , Li Chun‐Jie , Zhou Cheng , Liu Fei , Shen Jie‐Fei 
Published: July 2024

AbstractThe involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI‐ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI‐ION. Inhibition of Panx3 in the TG of CCI‐ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI‐ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS‐P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.