bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune checkpoint inhibitors for first‐line treatment of advanced non‐small‐cell lung cancer: A systematic review and network meta‐analysis
Authors: Peng Tzu‐Rong , Lin Hung‐Hong , Tsai Fang‐Pei , Wu Ta‐Wei 
Published: September 2021

AbstractObjectiveCurrently, several immune checkpoint inhibitors (ICIs) treatment for advanced non‐small‐cell lung cancer (NSCLC) have been investigated; their overall efficacy and safety remain unclear.MethodsWe searched electronic databases such as PubMed, EMBASE, and the Cochrane library. The randomized controlled trials (RCTs) that compared ICIs with or without chemotherapy to chemotherapy in advanced NSCLC. We collected and compaired thier parameters, including overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and treatment‐related adverse events (TRAEs) of grade ≥3.ResultsA total of 15 RCTs involving 8869 patients with NSCLC were included. Pembrolizumab plus platinum‐based chemotherapy had higher OS and PFS than platinum‐based chemotherapy (hazard ratio [HR] 0.55, 95% CI 0.46–0.67; HR 0.54, 95% CI 0.41–0.70, respectively). Pembrolizumab plus platinum‐based chemotherapy had higher ranked ORR than platinum‐based chemotherapy (odds ratio [OR] 2.92, 95% CI 1.99–4.22). In terms of OS, atezolizumab, pembrolizumab plus platinum‐based chemotherapy, and nivolumab plus ipilimumab ranked as the best treatments for patients with programmed death‐ligand 1 (PD‐L1) expression levels of ≥50%, 1–49%, and <1%, respectively. In terms of PFS, pembrolizumab plus platinum‐based chemotherapy ranked as the best treatment for patients with any PD‐L1 expression levels. However, ipilimumab plus platinum‐based chemotherapy, nivolumab plus platinum‐based chemotherapy, and atezolizumab plus platinum‐based chemotherapy have higher TRAEs of grade ≥3 than platinum‐based chemotherapy.ConclusionsPembrolizumab plus platinum‐based chemotherapy prevailed in rank in OS, PFS, and ORR benefit. The TRAEs of pembrolizumab plus platinum‐based chemotherapy were more than ICI monotherapy and chemotherapy.
Epigenetic treatment of behavioral and physiological deficits in a tauopathy mouse model
Authors: Wang Wei , Cao Qing , Tan Tao , Yang Fengwei , Williams Jamal B. , Yan Zhen 
Published: September 2021

AbstractEpigenetic abnormality is implicated in neurodegenerative diseases associated with cognitive deficits, such as Alzheimer's disease (AD). A common feature of AD is the accumulation of neurofibrillary tangles composed of hyperphosphorylated tau. Transgenic mice expressing mutant P301S human tau protein develop AD‐like progressive tau pathology and cognitive impairment. Here, we show that the euchromatic histone‐lysine N‐methyltransferase 2 (EHMT2) is significantly elevated in the prefrontal cortex (PFC) of P301S Tau mice (5–7 months old), leading to the increased repressive histone mark, H3K9me2, which is reversed by treatment with the selective EHMT inhibitor UNC0642. Behavioral assays show that UNC0642 treatment induces the robust rescue of spatial and recognition memory deficits in P301S Tau mice. Concomitantly, the diminished PFC neuronal excitability and glutamatergic synaptic transmission in P301S Tau mice are also normalized by UNC0642 treatment. In addition, EHMT inhibition dramatically attenuates the hyperphosphorylated tau level in PFC of P301S Tau mice. Transcriptomic analysis reveals that UNC0642 treatment of P301S Tau mice has normalized a number of dysregulated genes in PFC, which are enriched in cytoskeleton and extracellular matrix organization, ion channels and transporters, receptor signaling, and stress responses. Together, these data suggest that targeting histone methylation enzymes to adjust gene expression could be used to treat cognitive and synaptic deficits in neurodegenerative diseases linked to tauopathies.
The state in Chinese economic history
Authors: Qian Jiwei , Sng Tuan‐Hwee 
Published: September 2021

AbstractWe survey the recent economics and history literature on the Chinese state to investigate its role in China's long‐term socioeconomic development. We highlight three insights. First, unlike in Europe, where interstate competition helped give rise to capitalist states with high capacity, the Chinese state emerged from a different historical context. Second, the 18th‐ and 19th‐century Chinese state does not fit into the mould of a strong and extractive Oriental despotic state as once commonly believed. By conventional measures, early modern China had a weak state. Third, state building and centre‐local relations are two useful dimensions to understand development and change in China's recent history and political economy. To adapt China to a changing world, Chinese state builders embarked on a long process of state building from the late‐19th century through the Republican and Communist eras. Facilitated partly by regional decentralisation, the process now sees the Chinese state playing a substantially larger role in the economy and everyday life than any previous time in history.
Management of haematoma after thyroid surgery: systematic review and multidisciplinary consensus guidelines from the Difficult Airway Society, the British Association of Endocrine and Thyroid Surgeons and the British Association of Otorhinolaryngology, Head and Neck Surgery
Authors: Iliff H. A. , El‐Boghdadly K. , Ahmad I. , Davis J. , Harris A. , Khan S. , Lan‐Pak‐Kee V. , O’Connor J. , Powell L. , Rees G. , Tatla T. S. 
Published: September 2021

SummaryHaematoma after thyroid surgery can lead to airway obstruction and death. We therefore developed guidelines to improve the safety of peri‐operative care of patients undergoing thyroid surgery. We conducted a systematic review to inform recommendations, with expert consensus used in the absence of high‐quality evidence, and a Delphi study was used to ratify recommendations. We highlight the importance of multidisciplinary team management and make recommendations in key areas including: monitoring; recognition; post‐thyroid surgery emergency box; management of suspected haematoma following thyroid surgery; cognitive aids; post‐haematoma evacuation care; day‐case thyroid surgery; training; consent and pre‐operative communication; postoperative communication; and institutional policies. The guidelines support a multidisciplinary approach to the management of suspected haematoma following thyroid surgery through oxygenation and evaluation; haematoma evacuation; and tracheal intubation. They have been produced with materials to support implementation. While these guidelines are specific to thyroid surgery, the principles may apply to other forms of neck surgery. These guidelines and recommendations provided are the first in this area and it is hoped they will support multidisciplinary team working, improving care and outcomes for patients having thyroid surgery.
Can time to menopause be predicted?
Authors: Tanbo Tom G. , Fedorcsak Peter Z. 
Published: September 2021

AbstractMenopause represents the definite end of a woman’s reproductive life and the onset of a persistent hypoestrogenic state. This postmenopausal period will for most women last several decades. Although mean menopausal age seems to have increased somewhat during the last century, there is a significant individual variation in age at natural menopause. With efficient contraception, women of reproductive age can now, to some extent, choose when they want to have children. As a consequence of this and other sociodemographic changes, age at first birth has increased significantly over the last 50 years. It is well documented that long before a woman enters the menopausal transition and subsequent menopause, fertility declines and finally ceases. Being able to predict when a woman will enter menopause would therefore, from a reproductive perspective, be of major interest. Several sociodemographic, morphometric, and endocrine factors are associated with age at menopause or time to menopause. Unfortunately the sensitivity and specificity of these in predicting time to or age at menopause are low. Therefore, with the exception of anti‐Müllerian hormone measurements, either alone or in combination with chronological age close to menopause, there are as of now no reliable ways of predicting when a woman will enter menopause.
Comparison on the properties of bovine pericardium and porcine pericardium used as leaflet materials of transcatheter heart valve
Authors: Jin Chang , Zhao Li , Wu Zebin , Li Bin , Liu Ronghui , He Hongping , Wang Lizhen , Wang Weidong 
Published: September 2021

AbstractBackgroundIn order to obtain the smaller delivery diameter, porcine pericardium had been used as a substitute material of bovine pericardium for the leaflet materials of transcatheter heart valve (THV). However, the differences between them had not been fully studied. Therefore, this study compared the microstructure, biochemical and mechanical properties of two materials and hydrodynamics of THV made by the two materials in detail.MethodsIn this study, firstly, the microstructure of pericardium was analyzed by staining and scanning electron microscope; secondly, the biochemical properties of pericardium after different processes were compared by heat shrinkage temperature test, free amino and carboxyl concentration test, enzyme degradation test, subcutaneous implantation calcification analysis in rats; finally, the mechanical properties were evaluated by uniaxial tensile test before and after the pericardium being crimped, and then, the hydrodynamics of THV was studied according to the ISO5840 standard.ResultsCompared with bovine pericardium, after the same process, porcine pericardium showed a looser and tinier fiber bundle, a similar free carboxyl concentration, a lower resistance to enzyme degradation, a significantly lower calcification, bearing capacity and damage after being crimped, a better hydrodynamic and adaption with lower cardiac output and deformation of implantation position. Meanwhile the dehydration process of pericardium almost had preserved all the biochemical advantages of two materials.ConclusionIn this study, porcine and bovine pericardium showed some significant differences in biochemical, mechanical properties and hydrodynamics. According to the results, it was presumed that the thinner porcine pericardium might be more suitable for THV of right heart system. Meanwhile, more attention should be taken for the calcification of THV made by the bovine pericardium.
Pharmacokinetically‐guided dosing to improve the efficacy of brigatinib in non‐small cell lung cancer patients
Authors: Koele Simon E. , van Beek Stijn W. , van der Wekken Anthonie J. , Piet Berber , van den Heuvel Michel M. , ter Heine Rob 
Published: September 2021

Brigatinib was recently approved for the treatment of anaplastic lymphoma kinase‐positive non‐small cell lung cancer and is dosed according to a one‐dose‐fits‐all paradigm. We aimed to identify a pharmacokinetically‐guided precision dosing strategy to improve treatment response with brigatinib through simulations using a previously published pharmacokinetic‐pharmacodynamic model. Dosing strategies explored were the approved 180 mg QD; the highest tolerable dose tested in clinical trials: 240 mg QD; and two precision dosing strategies targeting the median trough concentrations following 180 mg QD, and 240 mg QD. We investigated the impact of alternative dosing regimens on progression‐free survival (PFS), overall survival (OS) and the probability of developing a grade ≥2 rash or grade ≥2 amylase increase. Median PFS and OS increased by 1.6 and 7.8 months, respectively between the currently approved dosing strategy and precision dosing to the median trough concentration of the 240 mg dosing strategy, with only a minor increase in the probability of developing toxicity.
‘'Ethno…graphy?!? I can't even say it”: Co‐designing training for ethnographic research for people with learning disabilities and carers
Authors: Mikulak Magdalena , Ryan Sara , Bebbington Pam , Bennett Samantha , Carter Jenny , Davidson Lisa , Liddell Kathy , Vaid Angeli , Albury Charlotte 
Published: September 2021

Accessible Summary

We are a team of academic researchers, people with learning disabilities and carers. We worked together to design training materials for people with learning disabilities and carers to work as co‐researchers on research projects.

The training was for doing a type of research called ethnography. When you do ethnography, you spend time with people to learn about their lives.

In this article, we describe what we did and what we learnt.

We think more people with learning disabilities and carers should be involved in research but many do not have the confidence to do it. Training can help with that.

We also think that ethnography is a type of research that can be easier to do than other types of research. This is because ethnography uses the skills lots of us already have the following: watching, listening and talking to people.

AbstractBackgroundThere is a strong ethical case and an urgent need for more participatory research practices in disability research but a lack of resources to support this. It is important to involve people with learning disabilities and carers at all stages, including when designing training for co‐research.MethodsWe co‐developed training materials to support people with learning disabilities and carers to work as ethnographic co‐researchers and for academic researchers to facilitate co‐research. We focused on what people with learning disabilities and carers thought was important to learn.FindingsWhilst not all types of research methods are easy to democratise, ethnographic observation is a research method that lends itself well to participatory co‐research.ConclusionsFor people to be able to meaningfully participate, research processes need to become more accessible and transparent. Training that considers the needs and priorities of people with learning disabilities and carers and addresses the confidence gap is key for meaningful co‐research.
MK‐6, a novel not‐α IL‐2, elicits a potent antitumor activity by improving the effector to regulatory T cell balance
Authors: Kobayashi Maki , Kojima Katsuhiko , Murayama Kazutaka , Amano Yuji , Koyama Takashi , Ogama Naoko , Takeshita Toshikazu , Fukuhara Tatsuro , Tanaka Nobuyuki 
Published: September 2021

AbstractIL‐2 is a pleiotropic cytokine that regulates immune cell homeostasis. Its immunomodulatory function has been used clinically as an active immunotherapy agent for metastatic cancers. However, severe adverse effects, including the vascular leak syndrome and the preferential stimulation of anti‐immunogenic Treg rather than effector T cells, have been obstacles. We newly designed a mutein IL‐2, Mutakine‐6 (MK‐6), with reduced IL‐2Rα–binding capability. MK‐6 induced comparable cell growth potential toward IL‐2Rβγ–positive T cells but was far less efficient in in vitro Treg proliferation and STAT5 activation. Unlike IL‐2, in vivo administration of MK‐6 produced minimal adverse effects. Using CT26 and B16F10‐syngeneic tumor models, we found MK‐6 was highly efficacious on tumor regression. Serum albumin conjugation to MK‐6 prolonged in vivo half‐life and accumulated in CT26 tumors, showing enhanced antitumor effect. Tumor‐infiltrating leukocytes analysis revealed that albumin‐fused MK‐6 increased the ratio of effector CD8+ T cells to CD4+ Treg cells. These results demonstrated that MK‐6 is an efficient immunomodulator potentially used for improved immunotherapy with decreased adverse effects and attenuated Treg stimulation.
Pinoresinol diglucoside alleviates ischemia/reperfusion‐induced brain injury by modulating neuroinflammation and oxidative stress
Authors: Zhang Yi , Lei Yuanbiao , Yao Xiaoxi , Yi Jiping , Feng Ganghua 
Published: September 2021

AbstractBrain ischemia/reperfusion (I/R) injury is a common pathological process after ischemic stroke. Pinoresinol diglucoside (PDG) has antioxidation and anti‐inflammation activities. However, whether PDG ameliorates brain I/R injury is still unclear. In this study, middle cerebral artery occlusion (MCAO) model was established with male C57BL/6 mice, and the mice were treated with 5 and 10 mg/kg PDG via intravenous injection, respectively. The neurological deficit, infarct volume, and brain water content were then evaluated. HE staining and Nissl staining were used to analyze neuron injury. Besides, enzyme‐linked immunosorbent assay and colorimetry assay were used to examine the level of inflammatory markers and oxidative stress markers, and Western blot was used to detect the expressions of p‐p65, Nrf2, and HO‐1. It was revealed that PDG could significantly alleviate the MCAO‐induced neurological dysfunction of the mice and reduce the infarct volume, brain water content, and neuron injury. PDG treatment decreased the levels of TNF‐α, IL‐1β, IL‐6, NO, ROS, and MDA, and significantly increased the activities of SOD, GSH, and GSH‐Px in the brain tissue of the mice. Additionally, PDG could repress the activation of p65 and promote Nrf2 and HO‐1 expressions. In conclusion, PDG exerts anti‐inflammatory and antioxidation effects via regulating the NF‐κB pathway and Nrf2/HO‐1 pathway, thereby reducing the I/R‐induced brain injury of mice.
The correlation between neonatal parameters and late‐onset inner ear disorders in congenital cytomegalovirus infection: a 10‐year population‐based cohort study
Authors: Wu Pei‐Hsuan , Lee Chia‐Yi , Huang Jing‐Yang , Yang Shun‐Fa , Shih Cheng‐Ping 
Published: September 2021

AbstractObjectiveTo evaluate the correlation of neonatal parameters with late‐onset sensorineural hearing loss (SNHL) and vestibular dysfunction in individuals with congenital cytomegalovirus (cCMV) infection using the National Health Insurance Research Database (NHIRD) in Taiwan.DesignRetrospective cohort study.SettingThe whole Taiwanese population.ParticipantsPatients with related diagnostic codes and examinations in their records were regarded as having cCMV infection. Each subject in that group was matched to 10 control individuals with noncongenital CMV infection on the basis of several neonatal parameters, including low gestational age, low birth weight, low Apgar score, maternal history of CMV infection and prolonged cCMV infection. A total of 5893 and 58 930 participants were enrolled in the study and control groups, respectively.Main outcome measuresThe main outcomes were the development of SNHL and the development of vestibular dysfunction within one year after birth as reflected by diagnostic codes and specific examinations. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of each primary outcome between the two groups.ResultsOverall, 109 and 397 episodes of SNHL developed in the study group and the control group, respectively, and the study group demonstrated a significantly higher incidence of SNHL (adjusted HR: 2.56; 95% CI: 2.07–3.18). In addition, similar incidence rates of vestibular dysfunction were found in the study group and the control group, with 7 and 90 events, respectively (adjusted HR: 0.77; 95% CI: 0.36–1.67). In subgroup analyses, a higher incidence of SNHL was correlated with lower gestational age (GA) (adjusted HR: 2.09; 95% CI: 1.29–3.39), lower birth weight (BW) (adjusted HR: 2.05; 95% CI: 1.28–3.30) and prolonged cCMV infection (adjusted HR: 3.92; 95% CI: 1.95–7.88).ConclusionsLow GA, low BW and a long disease course are significantly correlated with late‐onset SNHL in cCMV infection.
Do or doughnut: A systematic review and pooled analysis on the utility of pathological evaluation of the anastomotic doughnut in oncological colorectal operations
Authors: Wlodarczyk Jordan , Gaur Kshitij , Mertz Kevin , Wickham Carey , Mirza Kasim L. , Hsieh Christine , Cologne Kyle G. 
Published: September 2021

AbstractAimEnd‐to‐end anastomosis staplers are frequently used in colorectal surgery, generating two anastomotic doughnuts. Whether pathological evaluation of the doughnut changes clinical practice remains unclear. We aim to identify any effects of pathological evaluation of anastomotic doughnuts after oncological colorectal surgery.MethodWe performed a systematic literature search utilizing PubMed, Clinicaltrials.gov, Cochrane, Embase and Web of Science databases and selected studies on evaluation of the anastomotic doughnut after oncological colorectal surgery with stapled end‐to‐end anastomosis. Outcome measures included: involved distal margin on the oncological sample, histological involvement of the doughnut, clinical change in management from a positive doughnut and study recommendations.ResultsOf the 5761 studies identified, eight studies encompassing 1754 patients were evaluated. Most operations were for primary colon (37.5%) or rectal adenocarcinoma (37.5%). Incidence of distal margin involvement of the oncological sample was reported in three papers, with six positive cases (1.1%). Of the 1754 doughnut pairs evaluated, five were positive for neoplasia (0.29%), three for adenomas (0.18%) and one for metaplastic polyp (0.06%), none of which changed postoperative treatment. Four studies recommended abandoning routine histopathological evaluation of anastomotic doughnuts, while the remaining four recommended evaluation only under certain criteria, including gross distal margin <2 cm (one study), gross distal margin <3 cm (one study), tumours undetected on gross examination (one study), ‘histologically aggressive cancers’ or grossly involved distal margin (one study).ConclusionRoutine evaluation of anastomotic doughnuts should be reconsidered, as <1% are positive for neoplasia. Exceptions may include specific scenarios where histopathology is likely to be clinically useful.
Influence of donor and recipient hepatitis B virus infection on long‐term outcomes after kidney transplantation
Authors: Yuan Qing , Haque Omar , Hong Shanjuan , Ortiz Andric , Bethea Emily D. , Sise Meghan E. , Markmann James F. , Elias Nahel 
Published: September 2021

AbstractBackgroundThe demand for transplantable kidneys continues to outstrip supply, and the risk of donor‐derived infection limits utilization. The effect of donor or recipient HBV status, defined by surface antigen (HBsAg) positivity, on long‐term survival outcomes of kidney transplant (KT) is unknown.MethodsWe conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D–R, D–R+, and D+R–. Pairwise comparisons of patient survival (PS) and all‐cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients.ResultsOur findings showed that there were no statistically significant differences in PS and GS among D–R, D–R+, and D+R–groups, nor was the patient or GS different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg– donors.ConclusionsHBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary.