bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enpatoran in COVID‐19 pneumonia: Safety and efficacy results from a phase II randomized trial
Authors: McKinnon John E. , Santiaguel Joel , Murta de Oliveira Claudia , Yu Dongzi , Khursheed Mukhy , Moreau Flavie , Klopp‐Schulze Lena , Shaw Jamie , Roy Sanjeev , Kao Amy H. ,   the ANEMONE Study Team
Published: October 2023

AbstractEnpatoran is a selective inhibitor of toll‐like receptors 7 and 8 (TLR7/8) that potentially targets pro‐inflammatory pathways induced by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). A phase II study conducted in Brazil, the Philippines, and the USA during the early pandemic phase assessed the safety and efficacy of enpatoran in patients hospitalized with COVID‐19 pneumonia (NCT04448756). A total of 149 patients, who scored 4 on the World Health Organization's (WHO) 9‐point ordinal severity scale, were randomized 1:1:1 and received enpatoran 50 mg (n = 54) or 100 mg (n = 46), or placebo (n = 49) twice daily (b.i.d.) for 14 days plus standard of care. The primary objectives were safety and time to recovery (WHO 9‐point scale ≤3). Clinical deterioration (WHO 9‐point scale ≥ 5) was a key secondary objective. Treatment‐emergent adverse events (TEAEs) were comparable across groups (56.5%–63.0%). Treatment‐related TEAEs were numerically higher with enpatoran 50 mg (14.8%) than 100 mg (10.9%) or placebo (8.2%). Serious TEAEs were numerically lower with enpatoran (50 mg 9.3%, 100 mg 2.2%) than placebo (18.4%). The primary efficacy objective was not met; median time to recovery was 3.4–3.9 days across groups, with placebo‐treated patients recovering on average faster than anticipated. Clinical deterioration event‐free rates up to Day 7 were 90.6%, 95.6%, and 81.6% with enpatoran 50 mg, 100 mg, and placebo, respectively. Enpatoran was well tolerated by patients acutely ill and hospitalized with COVID‐19 pneumonia. Positive signals in some secondary end points suggested potential beneficial effects, supporting further evaluation of enpatoran in patients with hyperinflammation due to infection or autoimmunity.
Role of DNA ploidy in diagnosis and prognosis of high‐grade cervical intraepithelial neoplasia: A prospective cohort study
Authors: Pogere Adriane , Costa Ane Francyne , Pasinato Ana Paula Beltrame Farina , Machado Marcos José , de Miranda Onofre Fabiana Botelho , Onofre Alexandre Sherlley Casimiro 
Published: October 2023

AbstractObjectiveTo compare the sensitivity and specificity of DNA ploidy with cytology, human papillomavirus (HPV) testing and colposcopy in diagnosis of high‐grade cervical intraepithelial neoplasia (CIN) and to assess the role of aneuploidy in cervical lesions with the worst prognosis. A prospective observational cohort study was conducted on 254 women with altered colpocytology.MethodsColposcopy, biopsy, DNA‐ICM and HPV examinations were applied to cervical cytological and histological samples. Participants were evaluated every 6 months and divided into two groups: ‘Harm’ and ‘No‐harm’. Logistic regression and multivariate COX model were used to identify independent risk factors for diagnosis and prognosis of high‐grade CIN, and ROC curve to assess the sensitivity and specificity of methods.ResultsVariables ‘age greater than or equal to 30 years’, ‘lesion size greater than 20%’, ‘aneuploidy’ and ‘HPV 16’ were associated with diagnosis of high‐grade CIN and ‘aneuploidy’ and ‘women living with HIV’, with a worse prognosis. Agreement for colposcopy was good, with a sensitivity of 79.3% and specificity of 94.4%; DNA‐ICM and cytology were moderate, with sensitivity of 74.6% and 72.3% and specificity of 85.3% and 76.1%, respectively. High‐risk HPV and HPV 16 tests were weak, with sensitivity of 75.0% and 43.75% and specificity of 50.0% and 88.64%, respectively.ConclusionsIn relation to high‐grade CIN diagnosis, DNA‐ICM presented similar sensitivity and specificity to cytology and high‐risk HPV test when associated with HPV 16. Regarding prognosis, this research certifies that aneuploidy is considered a predictor of more severe cervical injury.
Fifteen years of real‐world data on the use of vigabatrin in individuals with infantile epileptic spasms syndrome
Authors: Kuchenbuch Mathieu , Lo Barco Tommaso , Chemaly Nicole , Chiron Catherine , Nabbout Rima 
Published: October 2023

AbstractObjectiveThis study was undertaken to evaluate our treatment algorithm for infantile epileptic spasms syndrome (IESS) used between 2000 and 2018. We initiated vigabatrin (VGB), and steroids were added if the electroclinical response (spasms and electroencephalogram [EEG]) to VGB was not obtained or incomplete.MethodsIndividuals with IESS treated with VGB were recruited from our hospital clinical data warehouse based on electronic health records (EHRs) generated since 2009 and containing relevant keywords. We confirmed the diagnosis of IESS. Clinical, EEG, imaging, and biological data were extracted from the EHRs. We analyzed factors associated with short‐term response, time to response, relapse, time to relapse of spasms, and the presence of spasms at last follow‐up.ResultsWe collected data from 198 individuals (female: 46.5%, IESS onset: 6 [4.5–10.3] months, follow‐up: 4.6 [2.5–7.6] years, median [Q1–Q3]) including 129 (65.2%) with identifiable etiology. VGB was started 17 (5–57.5) days after IESS diagnosis. A total of 113 individuals were responders (57.1% of the cohort), 64 with VGB alone and 38 with VGB further combined with steroids (56.6% and 33.6% of responders, respectively). Among responders, 33 (29%) experienced relapses of spasms, mostly those with later onset of spasms (p = .002) and those who received VGB for <24 months after spasms cessation compared to a longer duration on VGB (45% vs. 12.8%, p = .003). At follow‐up, 92 individuals were seizure‐free (46.5% of the whole cohort), including 26 free of therapy (13.1%). One hundred twelve individuals (56.6%) were still receiving VGB, with a duration of 3.2 (1.75–5.7) years.SignificanceOur sequential protocol introducing VGB then adding steroids is an effective alternative to a combined VGB–steroids approach in IESS. It avoids steroid‐related adverse events, as well as those from VGB–steroid combination. According to our data, a period of 7 days seems sufficient to assess VGB response and enables the addition of steroids rapidly if needed. Continuing VGB for 2 years may balance the risk of relapse and treatment‐induced adverse events.
RETRACTED: Effects of laparoscopic splenectomy on surgical site wound infection in patients with spleen rupture: A meta‐analysis
Authors: Deng Yin , Zhang Xianhuan , Li Aiming , Zhao Ye , Ye Liya 
Published: October 2023

AbstractA meta‐analysis was performed to compare the effects of laparoscopic splenectomy (LS) and open splenectomy (OS) for splenic rupture on postoperative surgical site wound infections and postoperative complications. A comprehensive computerised search was conducted for studies comparing LS with OS for the treatment of splenic rupture in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases, with the search including studies published in any language between the creation of the databases and August 2023. Two researchers independently screened the literature and extracted the data. Literature quality was assessed using the Newcastle‐Ottawa Scale, and the included data were collated and analysed using Stata 17.0 software for meta‐analysis. Twenty‐two studies involving 1545 patients were included. LS was superior to OS in the following aspects: reduced risk of postoperative surgical site wound infection (OR = 0.19, 95% CI: 0.11–0.34, p = 0.000), shortened hospital stay (standardised mean difference = −1.73, 95% CI: −2.05 to −1.40, p = 0.000), and reduced postoperative complication rate (OR = 0.22, 95% CI: 0.16–0.31, p = 0.000). Compared with OS, LS has a lower rate of postoperative wound infection, shorter hospital stay, and reduced rate of postoperative complications. LS is safe and effective for the treatment of splenic rupture and can be promoted clinically.
The association between metabolic syndrome and insulin resistance with risk of cardiovascular events in different states of cardiovascular health status
Authors: Hosseinpour‐Niazi Somayeh , Afaghi Siamak , Hadaegh Parto , Mahdavi Maryam , Farhadnejad Hossein , Tohidi Maryam , Mirmiran Parvin , Azizi Fereidoun , Hadaegh Farzad 
Published: October 2023

ABSTRACTAims/IntroductionThe aim was to examine the joint effect of metabolic syndrome (MetS) and insulin resistance (IR) with ideal cardiovascular health (iCVH) status on incident cardiovascular diseases (CVDs).Materials and MethodsThe study included 6,240 Iranian adults ≥30 years, free of prior cardiovascular disease. Ideal cardiovascular health was determined based on American Heart Association's Life Simple 7. Metabolic syndrome was defined according to the Joint Interim Statement Criteria, and insulin resistance was defined as HOMA‐IR ≥1.85 in women and ≥2.17 in men. Multivariable Cox proportional hazard ratios (HRs) were applied to examine the impact of metabolic syndrome, and insulin resistance at various levels of iCVH status.ResultsDuring the median follow‐up of 14.0 years, 909 cases of cardiovascular disease occurred. Metabolic syndrome and insulin resistance were significantly associated with incident cardiovascular disease events. In the poor and intermediate status, metabolic syndrome increased cardiovascular disease events with HRs of 1.83 and 1.57, respectively; the corresponding values for insulin resistance in the mentioned categories were 1.91 and 1.25, respectively (P values < 0.05). In the intermediate and poor iCVH status, hypertriglyceridemia was linked to a 40% and 35% higher risk of cardiovascular disease, the corresponding values for low HDL‐C was 20% and 60%, respectively (P values < 0.05). Although adding metabolic syndrome, its dyslipidemia and insulin resistance to iCVH status in both poor and intermediate status significantly improve the prediction of cardiovascular disease using net reclassification improvement (P values < 0.05), the value of C‐index did not change.ConclusionsMetabolic syndrome and the dyslipidemia component had a negligible but significant improvement in the prediction of cardiovascular disease among individuals with non‐optimal iCVH status.
Myelination‐ and migration‐associated genes are downregulated after phagocytosis in cultured oligodendrocyte precursor cells
Authors: Hamanaka Gen , Hernández Iván Coto , Takase Hajime , Ishikawa Hidehiro , Benboujja Fouzi , Kimura Shintaro , Fukuda Norito , Guo Shuzhen , Lok Josephine , Lo Eng H. , Arai Ken 
Published: October 2023

AbstractIn the central nervous system, microglia are responsible for removing infectious agents, damaged/dead cells, and amyloid plaques by phagocytosis. Other cell types, such as astrocytes, are also recently recognized to show phagocytotic activity under some conditions. Oligodendrocyte precursor cells (OPCs), which belong to the same glial cell family as microglia and astrocytes, may have similar functions. However, it remains largely unknown whether OPCs exhibit phagocytic activity against foreign materials like microglia. To answer this question, we examined the phagocytosis activity of OPCs using primary rat OPC cultures. Since innate phagocytosis activity could trigger cell death pathways, we also investigated whether participating in phagocytosis activity may lead to OPC cell death. Our data shows that cultured OPCs phagocytosed myelin‐debris‐rich lysates prepared from rat corpus callosum, without progressing to cell death. In contrast to OPCs, mature oligodendrocytes did not show phagocytotic activity against the bait. OPCs also exhibited phagocytosis towards lysates of rat brain cortex and cell membrane debris from cultured astrocytes, but the percentage of OPCs that phagocytosed beta‐amyloid was much lower than the myelin debris. We then conducted RNA‐seq experiments to examine the transcriptome profile of OPC cultures and found that myelination‐ and migration‐associated genes were downregulated 24 h after phagocytosis. On the other hand, there were a few upregulated genes in OPCs 24 h after phagocytosis. These data confirm that OPCs play a role in debris removal and suggest that OPCs may remain in a quiescent state after phagocytosis.image
A systematic review and thematic synthesis of inpatient nursing staff experiences of working with high‐risk patient behaviours
Authors: Richardson Velmans Samuel , Joseph Christiana , Wood Lisa , Billings Jo 
Published: October 2023

AbstractIntroductionNursing staff are frequently exposed to high‐risk patient behaviours within inpatient health services, yet staff commonly report a lack of training and support in managing these behaviours.AimThe aim of the study was to examine nursing staff experiences of high‐risk behaviours in inpatient mental health settings.MethodsFour electronic databases (CINAHL, Medline, PsycINFO, EMBASE) were searched. The protocol for this review was prospectively registered in PROSPERO (Ref: CRD42022334739). A meta‐synthesis of nursing staff's experiences of high‐risk behaviours in inpatient mental health settings was conducted.ResultsWe identified 30 eligible studies. Six themes were constructed from the meta‐synthesis: the social contract of care; the function of risk behaviours; the expectation of risk; risk as a relational concept; navigating contradictions in care; the aftermath.DiscussionNursing staff conceptualize risk as a meaningful behaviour shaped by patient, staff and environmental factors. Managing risk is an ethical dilemma for nursing staff and they require more training and support in ethical risk decision‐making.Implications for PracticeInpatient mental healthcare services should formulate and manage risk as a relational concept comprising staff, patient and environmental factors. Future research and clinical practice should place further consideration on the varied experiences of different types of risk behaviours.Relevance StatementNursing staff are frequently exposed to high‐risk patient behaviours within inpatient health services, yet staff commonly report a lack of training and support in managing these behaviours. This systematic review offers insights into how high‐risk behaviours are experienced by nursing staff and makes recommendations about how to improve the understanding and management of them. Inpatient mental healthcare services should formulate and manage risk as a relational concept comprising staff, patient and environmental factors. Future research and clinical practice should place further consideration on the varied experiences of different types of risk behaviours.
Granzyme B promotes matrix metalloproteinase‐1 (MMP‐1) release from gingival fibroblasts in a PAR1‐ and Erk1/2‐dependent manner: A novel role in periodontal inflammation
Authors: Ben‐Eltriki Mohamed , Ahmadi Amir Reza , Nakao Yuya , Golla Kalyan , Lakschevitz Flavia , Häkkinen Lari , Granville David J. , Kim Hugh 
Published: October 2023

AbstractObjectiveTo gain insights into how proteases signal to connective tissues cells in the periodontium.BackgroundThe connective tissue degradation observed in periodontitis is largely due to matrix metalloproteinase (MMP) release by gingival fibroblasts. Granzyme B (GzmB) is a serine protease whose role in periodontitis is undefined.MethodsHuman gingival crevicular fluid (GCF) samples were obtained from sites with periodontal disease and healthy control sites. GzmB was quantified in the GCF ([GzmB]GCF) by ELISA. Gingival fibroblasts (GF) were cultured in the presence or absence of recombinant GzmB. Culture supernatants were analyzed by ELISA to quantify GzmB‐induced release of interstitial collagenase (MMP‐1). In some experiments, cells were pre‐treated with the inhibitor PD98059 to block MEK/ERK signaling. The protease‐activated receptor‐1 (PAR‐1) was blocked with ATAP‐2 neutralizing antibody prior to GzmB stimulation. Systemic MMP‐1 levels were measured in plasma from wild‐type (WT) and granzyme‐B‐knockout (GzmB−/−) mice.ResultsThe [GzmB]GCF in human samples was ~4–5 fold higher at sites of periodontal disease (gingivitis/periodontitis) compared to healthy control sites, suggesting an association between GzmB and localized matrix degradation. GzmB induced a ~4–5‐fold increase in MMP‐1 secretion by cultured fibroblasts. GzmB induced phosphorylation of Erk1/2, which was abrogated by PD98059. GzmB‐induced upregulation of MMP‐1 secretion was also reduced by PD98059. Blockade of PAR‐1 function by ATAP‐2 abrogated the increase in MMP‐1 secretion by GF. Circulating MMP‐1 was similar in WT and GzmB−/− mice, suggesting that GzmB's effects on MMP‐1 release are not reflected systemically.ConclusionThese data point to a novel GzmB‐driven signaling pathway in fibroblasts in which MMP‐1 secretion is upregulated in a PAR1‐ and Erk1/2‐dependent manner.
Quantifying the roles of algal photosynthetic electron pathways: a milestone towards photosynthetic robustness
Authors: Burlacot Adrien 
Published: October 2023

SummaryDuring photosynthesis, electron transport reactions generate and shuttle reductant to allow CO2 reduction by the Calvin–Benson–Bassham cycle and the formation of biomass building block in the so‐called linear electron flow (LEF). However, in nature, environmental parameters like light intensity or CO2 availability can vary and quickly change photosynthesis rates, creating an imbalance between photosynthetic energy production and metabolic needs. In addition to LEF, alternative photosynthetic electron flows are central to allow photosynthetic energy to match metabolic demand in response to environmental variations. Microalgae arguably harbour one of the most diverse set of alternative electron flows (AEFs), including cyclic (CEF), pseudocyclic (PCEF) and chloroplast‐to‐mitochondria (CMEF) electron flow. While CEF, PCEF and CMEF have large functional overlaps, they differ in the conditions they are active and in their role for photosynthetic energy balance. Here, I review the molecular mechanisms of CEF, PCEF and CMEF in microalgae. I further propose a quantitative framework to compare their key physiological roles and quantify how the photosynthetic energy is partitioned to maintain a balanced energetic status of the cell. Key differences in AEF within the green lineage and the potential of rewiring photosynthetic electrons to enhance plant robustness will be discussed.
Reverse Lumbar Pedicle Screw in Oblique Lateral Interbody Fusion: A Novel Concept to Restrict Cage Subsidence
Authors: He Jinyue , Luo Fei , Fang Qing , Xu Jianzhong , Zhang Zehua 
Published: October 2023

ObjectiveCage subsidence is a common morbidity after oblique lumbar interbody fusion (OLIF), with risk of compromising clinical and radiographic outcomes. The study aims to describe an innovative reverse lumbar pedicle screw (RLPS) technique in OLIF and compare its effect on restricting cage subsidence with classical lateral fixation (LF) in radiological and clinical evaluation.MethodConsecutive patients having undergone single‐level OLIF‐LF/RLPS from 2018 to 2020 were retrospectively reviewed. In OLIF‐RLPS, the upper entry point was determined at the intersection between one horizontal line (1 cm above inferior endplate) and one vertical line (dissecting anterior and middle thirds of the vertebra) while the inferior entry point between one horizontal line (5 mm below superior endplate) and the same vertical line. Trajectories were from vertebrae reverse into contralateral pedicle. Radiological evaluation included disc height (DH) and segmental lordosis (SL); cage subsidence was evaluated by DH loss. Clinical assessment included visual analogue scale (VAS) and Oswestry disability index (ODI). Student t or Mann–Whitney U test was used for continuous variation according to normality analysis while Chi‐square test for category variation.ResultsA total of 29 patients had been enrolled in the study including 14 cases in the RLPS group and 15 cases in the LF group. The DH in the OLIF‐RLPS group had increased from the preoperative 9.07 ± 1.73 mm to 13.73 ± 1.83 mm postoperatively, without significant difference compared with the OLIF‐LF group during the perioperative, but decreased to 12.53 ± 1.74 mm in 3 months and maintained at 12.00 ± 1.45 mm in 12 months, significantly higher than the OLIF‐LF group (p < 0.05). At the last follow‐up, 7.1% (1/14) cases in the OLIF‐RLPS group had shown subsidence of grade I, significantly less than 46.7% (7/15) cases in the OLIF‐LF group. Pain and disability had improved similarly in two groups, without significant difference detected between two groups at the last follow‐up.ConclusionRLPS technique with modified entry points and prolonged trajectory could effectively restrict cage subsidence in OLIF postoperatively compared with traditional lateral fixation.
Genetic and dermoscopic findings in a case series of children with oculocutaneous albinism
Authors: Liñán‐Barroso Juan Manuel , Mantrana‐Bermejo María Eugenia , Durán‐Romero Antonio José , Ortiz‐Álvarez Juan , Monserrat‐García María Teresa , Jiménez‐Thomas Guillermo José , Conejo‐Mir Sánchez Julián , Bernabéu‐Wittel José 
Published: October 2023

AbstractOculocutaneous albinism (OCA) is a genetic disease caused by disorders in melanin synthesis or distribution. In this descriptive study conducted in a tertiary care pediatric hospital, patients with a clinical diagnosis of OCA and genetic study were retrospectively recruited and underwent dermatological and ophthalmological exam, including optical coherence tomography (OCT) and digital dermoscopy. Our findings revealed milder OCA phenotypic expression in individuals harboring single pathogenic mutations in conjunction with polymorphisms, as well as in those with mutations of uncertain significance. Regardless OCA subgroup, severe phenotypes of OCA were associated with a higher number of mutations/polymorphisms in melanin biosynthesis genes and paler dermoscopic patterns, such as vascular pattern, which was the most common pattern in our series.
Oocyte recovery after overnight ovary transport provides an alternative source of cumulus oocyte complexes that are competent to produce live piglets
Authors: Spate Lee D. , Yin Jie , Sammel Lauren , Prather Randall S. , Redel Bethany K. 
Published: October 2023

AbstractCOVID‐19 impacted abattoirs worldwide. The processing lines became a hotspot for the spread of COVID‐19 resulting in plant restructuring and ultimately a critical loss of pig material for research. Commercial sources of pig oocytes are available but are costly and companies were already operating at a maximum capacity for supplying the oocyte needs around the United States. Here, we provide an alternative source of oocytes that are competent to produce live, healthy piglets.
Functions tiling simultaneously with two arithmetic progressions
Authors: Etkind Mark Mordechai , Lev Nir 
Published: October 2023

AbstractWe consider measurable functions on that tile simultaneously by two arithmetic progressions and at respective tiling levels and . We are interested in two main questions: what are the possible values of the tiling levels , and what is the least possible measure of the support of ? We obtain sharp results which show that the answers depend on arithmetic properties of and , and in particular, on whether the numbers are rationally independent or not.