bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two multimodal intramuscular anaesthetic protocols in uncooperative feline patients: effects on sedation and echocardiographic measurements
Authors: Bagardi Mara , Locatelli Chiara , Brambilla Paola G , Ghilardi Sara , Rabbogliatti Vanessa , Amari Martina , Casiraghi Silvia , Ravasio Giuliano , Galimberti Luigi , Brioschi Federica A
Published: February 2023

Objectives

The aims of this study were to compare the sedative effect, feasibility of venous angiocatheter placement and influence on heart rate (HR), systemic blood pressure (SBP) and echocardiographic variables of two multimodal anaesthetic protocols in uncooperative cats; and to compare their influence on HR, SBP and echocardiographic variables 20 mins after sedation and after elective ovariectomy.

Methods

Eighteen stray female cats randomly received intramuscular (IM) ketamine (2 mg/kg) and methadone (0.3 mg/kg) plus dexmedetomidine (7 µg/kg; group D, n = 9) or alfaxalone (2 mg/kg; group A, n = 9). A sedation score (0–15 [from none to good sedation]) was assigned at 5 mins, 10 mins, 15 mins and 20 mins after IM injection. Venous angiocatheter placement and echocardiographic examination feasibility scores (both from 0 to 3 [from very difficult to very easy]) were recorded at 20 mins. Echocardiography, HR and blood pressure measurements (Doppler and oscillometric methods) were performed at 20 mins and at the end of surgery.

Results

Sedation and angiocatheter feasibility scores did not differ significantly between groups ( P >0.05); the feasibility score of echocardiographic examination was higher in cats in group D ( P = 0.01). HR was higher in group A at 20 mins and after surgery ( P <0.05). The systolic arterial pressure obtained with the Doppler method was statistically significantly higher in cats in group D than in group A at 20 mins ( P = 0.01), while postoperatively there were no differences between groups. Cats in group D showed significantly higher atrial diameters ( P <0.05) and slower atrial flows ( P = 0.04) compared with group A; ventricular thickness and atrial function did not differ between groups ( P >0.05). Most echocardiographic variables were not different at 20 mins vs postoperatively.

Conclusions and relevance

Both protocols allowed for effective sedation; however, cats in group D presented alterations in some echocardiographic measurements; the use of alfaxalone, combined with ketamine and methadone, is recommended to obtain a reliable echocardiographic evaluation in uncooperative cats.
Disbond detection of honeycomb sandwich structure through laser ultrasonics using signal energy map and local cross-correlation
Authors: Dong Zeyu , Chen Weikun , Saito Osamu , Okabe Yoji
Published: February 2023

Detecting disbonds in honeycomb sandwich structures using ultrasonics is challenging due to the complex wave propagation. This paper investigates the method for disbond quantification in honeycomb sandwich structures using laser ultrasonics. In the experiments on an aluminum specimen, the detection frequency range was determined by the local defect resonance (LDR) in the disbond regions. The energy maps of bandpass wavefields identified the locations of disbonds. To improve the results, a frequency-wavenumber analysis of the wavefields was performed. The wavenumber spectra were reconstructed by wavenumber filtering to strengthen the outline components for quantifying disbonds. Local cross-correlation (LCC) was proposed to show the outlines of disbonds and honeycomb cells, whose results agreed well with the X-ray imaging. Moreover, LCC could also quantify a disbond in the composite honeycomb sandwich structure. Consequently, combining energy maps and LCC results can effectively detect the locations and sizes of disbonds in honeycomb sandwich structures.
The Use of Janus Kinase Inhibitors for Lichen Planus: An Evidence-Based Review
Authors: Abduelmula Abrahim , Bagit Ahmed , Mufti Asfandyar , Yeung Katie C.Y. , Yeung Jensen
Published: February 2023

Background

Lichen Planus (LP) is a dermatological disorder characterized by violaceous papules that affect the cutaneous region, nails, scalp, and mucous membranes. Current molecular and clinical studies point to the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway as a potential effector of LP pathology.

Objective

This systematic review summarizes the current reported literature outcomes for patients receiving JAK inhibitors to treat LP.

Methods

MEDLINE and Embase were searched on 16 October, 2022, and 15 original articles were included, with 56 LP patients.

Results

(mean age: 54.5 years, range: 26-81 years, male: 26.8%). The treatment outcomes were included for the following JAK inhibitors: tofacitinib ( n = 30), baricitinib ( n = 16), ruxolitinib ( n = 12), and upadacitinib ( n = 2). Patient outcomes were classified into complete resolution, partial resolution, and no resolution. Patients achieving complete resolution represented 25% ( n = 4/16) in the baricitinib group, 10% ( n = 3/30) in the tofacitinib group, 16.7% ( n = 2/12) in the ruxolitinib group, and 100% (2/2) in the upadacitinib group. Partial resolution patients represented 31.3% ( n = 5/16) of baricitinib patients, 60% ( n = 18/30) of tofacitinib patients, and 83% ( n = 10/12) of ruxolitinib patients. 43.8% ( n = 7/16) of baricitinib patients and 10% ( n = 9/30) of tofacitinib patients had no resolution of lesions.

Conclusion

This review also highlights the significance of utilizing a uniform outcome measure for LP, as it aids in reporting more generalizable results, reduces reporting bias, and ultimately lead to improved clinical outcomes for LP patients.
Thermotemporalities, thermomasculinities: Uptime, downtime, and server heat in the digital Anthropocene
Authors: Gonzalez Monserrate Steven
Published: February 2023

Amid a warming planet and a surge in digital activity precipitated by COVID-19 lockdowns, the ecological impacts of cloud infrastructures are of increasing interest to scholars and publics. Deemed “essential workers,” data center operators maintain server uptime by keeping equipment cool (via air conditioning). Failure results in overheating and a state of service interruption called downtime. Drawing on ethnographic research in data centers, this article introduces the concept of thermotemporalities to illustrate how time, temperature, and expertise converge in novel formations. By attending to the embodied practices and discursive pronouncements of data center operators, I reveal how uptime (cold) and downtime (hot), a binary opposition, are performative genres rather than discrete referents. Emerging out of this dyadic interplay, I locate a species of aspirational identity I call thermomasculinities.
Data centers and the infrastructural temporalities of digital media: An introduction
Authors: Velkova Julia , Plantin Jean-Christophe
Published: February 2023

While data centres are predominantly studied via their spatial and territorial dimensions, we investigate this critical part of the contemporary Internet infrastructures via its temporalities and their multiple mediations. With this introduction and the articles of this special issue, we collectively complement existing scholarship on critical data studies and media infrastructure by investigating the role that data infrastructure plays in shaping the temporalities of data. Focusing on data centres, the contributors analyze the vast infrastructural assemblage that supports such temporalities. The concept of timescapes (after Barbara Adam) guides us to organize the contributions to this special issue along the analysis of three infrastructural timescapes of data—socio-economic, elemental, and transitory—to reveal new facets of the politics of time in the data economy.
When do we go from here? Data center infrastructure labor, jobs, and work in economic development time and temporalities
Authors: Mayer Vicki
Published: February 2023

Regional authorities and development experts wax about data infrastructures’ importance to local labor, both in terms of modernizing the past and creating new jobs in the future. This data infrastructure time of labor and jobs establishes a temporality of a region, and its leadership, as on the way to a progressive and calculable future. Using the example of a Google hyperscale data center which leaders extolled in Groningen, in the Netherlands, we explore how data infrastructure time shapes the temporalities of the workers whose jobs were presumed to be founded and futured by this event. By exploring these relational chains of power in the political economy of data infrastructures, I illustrate the ways that work temporalities are connected to broader social, political, and ecological forces in the region, while also offering new methods in understanding what global infrastructure companies mean to regions outside of global cities.
Script-switching in Japanese pop culture: a social semiotic multimodal approach
Authors: Matsuda Yuki
Published: February 2023

This article explores the nature of multimodal meaning-making in writing by analyzing the script-switching used in Japanese pop culture. Japanese intermixes multiple script systems in one text. Although official and public documents follow standard orthographic conventions, creative works in pop culture texts freely and regularly break these norms by switching script types to create new meanings. However, while many previous works recognize the semiotic effects of script-switching, to this day, there is no systematic account for how and why such meaning-making operates. Notably, script-switching triggers meanings independent of linguistic meaning. Yet, scripts are a visual manifestation of language, so one cannot say they are independent of language. Accordingly, this work attempts to resolve this dilemma by exploring a social semiotic multimodal approach (see Van Leeuwen ‘Typographic meaning’, 2005, and ‘Towards a semiotics of typography’, 2006, and Stöckl ‘Typography: Body and dress of a text’, 2005), which claims the semiotic independence of typography and its interdependency with language. By recognizing the basic unit of the writing system as graphemes, the author argues that the Japanese script systems are categorized into four types of graphemes depending on the linguistic unit they relate to and she demonstrates how the visual unit of the grapheme and the linguistic unit interact in meaning-making. In this analysis, script-switching occurs when grapheme types are intentionally changed to foreground a visual meaning associated with each script system. This article shows that such a meaning reflects the historical development and discursive social practices of writing with multiple script systems throughout the history of the Japanese writing system.
The Bridging Effect of Artificial Dermis on Reconstruction of Skin Avulsion Injury
Authors: Lin Yun-Nan , Wang Yu-Chi , Lee Su-Shin , Hsieh Meng-Chien Willie , Lin Sin-Daw , Huang Shu-Hung , Lin Tsai-Ming , Kuo Yur-Ren
Published: February 2023

Skin avulsion wounds are expected to be swollen and tense after trauma, and skin perfusion can be compromised after primary closure, resulting in wound dehiscence and poor healing. The artificial dermis (AD) serves as a dermal regeneration template that is used to heal skin defects with secondary intention. Therefore, the aim of this study is to evaluate the effect of AD application on traumatic skin avulsion injuries compared to conventional primary closure. A retrospective cohort of 20 patients with skin avulsion injuries were included the study: ten patients were treated with AD and ten patients were managed with primary closure. When compared to the primary closure group, AD group had a shorter average healing time (58.40 ± 26.94 days V 65.50 ± 46.45 days) and significantly higher flap viability (92.00 ± 13.17% V 78.00 ± 13.98%; p = .03). In conclusion, AD is a promising material for the treatment of skin avulsion injury and produces better clinical results.
Preparedness and response of assisted living facilities toward COVID-19 infection control in Houston, Texas, USA
Authors: Oladimeji Abisola M , Afe Abayomi Joseph , Olumuyiwa Tolulope , Offiong Charlene , Turibekov Bakbergen , Aikulola Oluwayemisi , Persse Courtney , Deadmon Jahana , Hansen Kristine , Barron Christine , Vijayan Vijisha , Mora Wanda , Farris Jacob , Dean Krysta , Johnson Thomas , Gonzalez Juan , Mansaray Rahmatu , Short Kirstin
Published: February 2023

Background

Long-term care facilities (LTCFs) including assisted living facilities (ALFs) are hubs for high transmission and poor prognosis of COVID-19 among the residents who are more susceptible due to old age and comorbidities.

Aim

Houston Health Department conducted assessments of ALFs within the City of Houston to determine preparedness and existing preventive measures at the facilities.

Methods

Onsite assessments were conducted at ALFs using a modified CDC Infection Control Assessment and Response (ICAR) Tool. Data was obtained on IPC measures, training, testing, vaccination etc. Data was analyzed, frequencies generated, and bivariate associations determined.

Results

A total of 118 facilities were assessed and categorized into small scale 46 (39%), medium scale 47 (40%), and large scale 25 (21%). The facilities had 2431 residents and 2290 staff. Thirty-one (26%) facilities reported an outbreak in 2020, while 14 (12%) had an ongoing outbreak. Twenty-three (97%) large-scale and 12 (26%) small-scale facilities had COVID-19 testing program. Vaccination coverage among residents ranged from 99% in large-scale to 40% in small-scale facilities but was smaller among staff at 748 (45%) in large scale, 71 (36%) in small scale, and 193 (45%) in medium scale. While 24 (96%) large-scale and 34 (77%) of small-scale facilities conducted staff training staff on IPC practices, 22 (92%) of large-scale and 19 (56%) of small-scale facility staff demonstrated capacity ( p = 0.01), respectively. Visitor screening was done at 100% of large-scale and 80% of small-scale and the medium-scale ALFs.

Discussion

Assisted living facilities within the city of Houston are at various levels of preparedness and interventions with respect to COVID-19 response.
Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma – A 13-years experience from a tertiary care centre
Authors: Khosla Divya , Kapoor Rakesh , Singla Aditya K , Periasamy Kannan , Goyal Shikha , Madan Renu , Kumar Narendra , Behera Arunanshu , Singh Shrawan K , Bhadada Sanjay K , Walia Rama
Published: February 2023

Purpose

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm, usually diagnosed in advanced stage. Role and efficacy of adjuvant radiotherapy has not been well defined. The objective of this study is to describe the various clinical characteristics and prognostic factors affecting the survival of ACC along with the role radiotherapy on overall survival and relapse free survival.

Methods

A retrospective analysis of 30 patients registered between 2007 and 2019 was carried out. The medical records containing clinical and treatment details were analysed. Data was analysed using SPSS 25.0. Survival curves were computed using Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic factors affecting the outcome. A p value of less than 0.05 was considered to be statistically significant.

Results

The median age of patients was 37.5 years (range, 5–72 years). 20 patients were females. Twenty-six patients had advanced stage (III/IV) disease while only four patients presented in early stage. Twenty-six patients underwent total adrenalectomy. Eighty three percent patients received adjuvant radiation therapy. The median follow up was 35.5 months (range, 7 monthss-132months). The estimated three- and 5-years overall survival (OS) was 67.2% and 23.3%, respectively. Capsular invasion and positive margins were the independent prognostic factors influencing both OS and relapse free survival (RFS). Out of 25 patients who received adjuvant radiation, only three patients had local relapse.

Conclusion

ACC is a rare and aggressive neoplasm with majority of patients presenting in advanced stage. Surgical resection with negative margins remains the mainstay of treatment. Capsular invasion and positive margins are independent prognostic factors for survival. Adjuvant radiation reduces the risk of local relapse and is well tolerated. Radiation can be used effectively in adjuvant and palliative settings in ACC.
Faculty acceptance of the utilization of learning management systems in teaching
Authors: Asamoah Moses K. , Oheneba-Sakyi Yaw , Tagoe Michael
Published: February 2023

Despite huge investments in Ghanaian universities for e-learning education, there exist lecturers who struggle with the adoption and use of open-source Learning Management Systems (LMSs) in teaching. The purpose of this study was to investigate the dominant drivers of the adoption and usage of LMS by faculty to enhance e-learning education in universities in Ghana. The study tested selected variables in Innovation Diffusion Theory, the Technology Acceptance Model, and some constructs pertaining to Image, Subjective Norms, and Facilitating conditions, based on data from a census of 435 lecturers, which secured 283 completed questionnaires. The fit indices revealed a good fit between the measurement model and the data: (χ2 = 383.23, df = 271, p < .05; SRMR = 0.046; TLI = 0.965; CFI = 0.971; RMSEA = 0.038. The SEM results showed that the hypothesized model appropriately matched the data: (χ2 = 360.39, df = 253, p < .05; SRMR = 0.048; CFI = 0.971; TLI = 0.964; RMSEA = 0.040. The results obtained from the test of hypotheses revealed that Perceived Ease of Use had a positive and significant relationship with Actual Use (β = 0.45, p < .05). Compatibility also had a significantly positive relationship with Perceived Usefulness (β = 0.62, p < .05). The study concludes that the responsibility of university authorities for providing ICT infrastructure, regular training, and other incentives to enable their faculty to appreciate and engage the e-learning environment is at the core of a successful adoption of educational technologies. Among others, the study recommends that university authorities provide continuous training in LMS use for their teaching staff, especially the slow adopters and non-users, to encourage greater adoption and use.
Epilepsy Characteristics in Duchenne and Becker Muscular Dystrophies
Authors: Ramani Praveen Kumar , Fawcett Kindann , Guntrum Debra , Samuel Hallie , Ciafaloni Emma , Veerapandiyan Aravindhan
Published: February 2023

Dystrophinopathies cover a spectrum of X-linked muscle disorders including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and cardiomyopathy due to pathogenic variants in the DMD gene. Neuropsychiatric manifestations occur approximately in one-third of patients with dystrophinopathy. Epilepsy has been described. Here we report seizure and electroencephalographic features of boys with dystrophinopathy and epilepsy. This is a retrospective chart review of eight patients with dystrophinopathy and epilepsy seen at Arkansas Children's Hospital and University of Rochester Medical center. Six patients had DMD and two had BMD. Five patients had generalized epilepsy. Three patients had focal epilepsy and the seizures were intractable in two of them. Brain imaging was available for five patients and were within normal limits. EEG abnormalities were noted in six patients. Seizures were well controlled on the current antiepileptic medication regimen in all patients. Further research is needed to better elucidate the underlying mechanisms and genotype-phenotype correlations.
‘They’re part of what we are’: Interspecies belonging, animal life and farming practice on the Isle of Skye
Authors: Fry Tom
Published: February 2023

This article develops the concept of interspecies belonging: a process of co-habitation between humans and non-humans achieved through material, affective and situated practises. This dynamic is generative of an intimate, personal sense of belonging and a socio-spatial politics of belonging. The article is based on ethnographic fieldwork amongst hill farmers and the animals they live alongside on the Isle of Skye, North-West Scotland. It considers how farming work is an embodied and sensorial immersion in more-than-human worlds, undergirded by affective intensities that produce a feeling of being right with the world, but also of the farming self as producer of commodity goods. Within the fraught political ecologies of a post-productivist uplands, and the growing influence of nature conservation in farming life, they animate a political belonging aimed at protecting access to natural resources. I demonstrate how the imbrication of animal behaviours, mobilities and bodies within this dynamic of belonging shapes how they are understood as legitimate or illegitimate presences within upland landscapes. Through this, I consider how the recently reintroduced sea eagle is engaged with by farmers as an exemplar of exogenous institutional intervention that marginalises an already precarious way of life.
Stochastic fate decisions of HSCs after transplantation: early contribution, symmetric expansion, and pool formation
Authors: Radtke Stefan , Enstrom Mark R , Pande Dnyanada , Duke Elizabeth R , Cardozo Ojeda Erwing Fabian , Madhu Ravishankar , Owen Staci , Kanestrom Greta , Cui Margaret Lee , Perez Anai M , Schiffer Joshua T , Kiem Hans-Peter
Published: February 2023

Hematopoietic stem cells (HSCs) are assumed to be rare, infrequently dividing, long-lived, and not involved in immediate recovery after transplantation. Here we performed unprecedented high-density clonal tracking in nonhuman primates and found long-term persisting HSC clones to actively contribute during early neutrophil recovery and be the main source of blood production as early as 50 days post-transplant. Most surprisingly, we observed a rapid decline in the number of unique HSC clones, while persisting HSCs expanded undergoing symmetric divisions to create identical siblings and formed clonal pools ex vivo as well as in vivo. In contrast to the currently assumed model of hematopoietic reconstitution, we provide evidence for contribution of HSCs in short-term recovery as well as symmetric expansion of individual clones into pools. These findings provide novel insights into HSC biology informing the design of HSC transplantation and gene therapy studies.
Dual targeting of CD19 and CD22 with Bicistronic CAR-T cells in Patients with Relapsed/Refractory Large B Cell Lymphoma
Authors: Roddie Claire , Lekakis Lazaros J. , Marzolini Maria A. V. , Ramakrishnan Aravind , Zhang Yiyun , Hu Yanqing , Peddareddigari Vijay G R , Khokhar Nushmia Z , Chen Robert W , Basilico Silvia , Raymond Meera , Arce Vargas Frederick , Duffy Kevin , Brugger Wolfram , O'Reilly Maeve , Wood Leigh , Linch David , Peggs Karl S , Bachier Carlos , Budde Elizabeth Lihua , Batlevi Connie Lee , Bartlett Nancy L. , Irvine David , Tholouli Eleni , Osborne Wendy , Ardeshna Kirit M , Pule Martin
Published: February 2023

Relapse following CD19-directed chimeric antigen receptor T-cells (CAR-T) for relapsed/refractory large B-cell lymphoma (r/r LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multi-antigen targeting and PD-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in r/r LBCL as inpatient or outpatient therapy (NCT03289455, https://clinicaltrials.gov/ct2/show/NCT03289455). Endpoints include toxicity (primary) and response rates (secondary). AUTO3 was manufactured for 62 patients using autologous leukapheresis, modified with a bicistronic transgene. 52 patients received AUTO3 (7/52,50x106; 45/52,150-450x106) and 48/52 received pembrolizumab. Median age was 59 years (range,27-83) and 46/52 had stage III/IV disease. Median follow-up was 21.6 months (range,15.1-51.3) at last data cut (Feb 28, 2022). AUTO3 was safe: grade 1-2 and grade 3 CRS affected 18/52 (34.6%) and 1/52 (1.9%) patients, neurotoxicity arose in 4 patients (2/4, grade 3-4), HLH affected 2 patients, and no Pembrolizumab-associated autoimmune sequalae were observed. On this basis, outpatient administration was tested in 20 patients, saving a median of 14 hospital days/patient. AUTO3 was effective: overall response rates were 66% (48.9%, CR; 17%, PR). For patients with CR, median DOR was not reached, with 54.4% (CI: 32.8, 71.7) projected to remain progression-free beyond 12 months after onset of remission. DOR for all responding patients was 8.3 months (95% CI: 3.0, NE) with 42.6% projected to remain progression-free beyond 12 months after onset of remission. Overall, AUTO3 +/- pembrolizumab for r/r LBCL was safe, lending itself to outpatient administration, and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion/persistence in vivo, and selection of CAR binders active at low antigen densities.
5-Year Follow-Up Supports Curative Potential of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma (ZUMA-1)
Authors: Neelapu Sattva S. , Jacobson Caron A. , Ghobadi Armin , Miklos David B , Lekakis Lazaros J. , Oluwole Olalekan O. , Lin Yi , Braunschweig Ira , Hill Brian T. , Timmerman John M. , Deol Abhinav , Reagan Patrick M , Stiff Patrick Joseph , Flinn Ian W. , Farooq Umar , Goy Andre , McSweeney Peter , Munoz Javier , Siddiqi Tanya , Chavez Julio C. , Herrera Alex F. , Bartlett Nancy L. , Bot Adrian A. , Shen Rhine R. , Dong Jinghui , Singh Kanwarjit , Miao Harry , Kim Jenny J. , Zheng Yan , Locke Frederick L.
Published: February 2023

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we aimed to assess survival and safety in ZUMA-1 after 5 years of follow-up. Eligible adults with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) received lymphodepleting chemotherapy followed by axi-cel infusion targeted at 2×106 cells/kg. Investigator-assessed response, updated survival, safety, and pharmacokinetic outcomes were assessed in treated patients. The objective response rate in the 101 treated patients was 83% (58% complete response rate), and with a median follow-up of 63.1 months, responses were ongoing at data cutoff in 31%. Median overall survival (OS) was 25.8 months and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91%. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. ClinicalTrials.gov, number NCT02348216
Genome-wide mapping of GlnR-binding sites reveals the global regulatory role of GlnR in controlling the metabolism of nitrogen and carbon in Paenibacillus polymyxa WLY78
Authors: Wang Tianshu , Zhao Xiyun , Wu Xinyuan , Chen Sanfeng
Published: February 2023

Background

Paenibacillus polymyxaWLY78 is a Gram-positive, endospore-forming and N2-fixing bacterium. Our previous study has demonstrated that GlnR acts as both an activator and a repressor to regulate the transcription of thenif(nitrogenfixation) operon (nifBHDKENXhesAnifV) according to nitrogen availability, which is achieved by binding to the two GlnR-binding sites located in thenifpromoter region. However, further study on the GlnR-mediated global regulation in this bacterium is still needed.

Results

In this study, global identification of the genes directly under GlnR control is determined by using chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assays (EMSA). Our results reveal that GlnR directly regulates the transcription of 17 genes/operons, including anifoperon, 14 nitrogen metabolism genes/operons (glnRA,amtBglnK,glnA1,glnK1,glnQHMP,nasA,nasD1,nasD2EF,gcvH,ansZ,pucR,oppABC,appABCDFanddppABC)and 2 carbon metabolism genes (ldh3andmaeA1). Except for theglnRAandnifoperon, the other 15 genes/operons are newly identified targets of GlnR. Furthermore, genome-wide transcription analyses reveal that GlnR not only directly regulates the expression of these 17 genes/operons, but also indirectly controls the expression of some other genes/operons involved in nitrogen fixation and the metabolisms of nitrogen and carbon.

Conclusion

This study provides a GlnR-mediated regulation network of nitrogen fixation and the metabolisms of nitrogen and carbon.
Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity
Authors: Liu Yulan , Meng Yang , Zhou Chenliang , Yan Juanjuan , Guo Cuiping , Dong Weiguo
Published: February 2023

Background

Neuroinflammation plays a critical role in amyloid-β (Aβ) pathophysiology. The cytokine interleukin-17A (IL-17) is involved in the learning and memory process in the central nervous system, and its level was reported to be increased in Alzheimer's disease (AD) brains, while the effect of IL-17 on the course of Aβ has not been well defined.

Methods

Here, we used APP/PS1 mice to detect the IL-17 expression level. Primary hippocampal neurons were treated with IL-17, and immunofluorescence was used to investigate whether IL-17 induced neuronal damage. At the same time, male C57BL/6 mice were injected with Aβ42 to mimic the Aβ model. Then, IL-17 neutralizing antibody (IL-17Ab) was injected into the lateral ventricle, and the open-field test, novel objective recognition test, and fear conditioning test were used to detect cognitive function. Long-term potentiation (LTP) was used to assess synaptic plasticity, molecular biology technology was used to assess the IL-17/TRAF6/NF-κB pathway, and ELISA was used to detect inflammatory factors.

Results

Altogether, we found that IL-17 was increased in APP/PS1 mice and induced neural damage by administration to primary hippocampal neurons. Interestingly, using Aβ42 mice, the results showed that the level of IL-17 was increased in Aβ42 model mice, and IL-17Ab could ameliorate Aβ-induced neurotoxicity and cognitive decline in 10 C57BL/6 mice by downregulating the TRAF6/NF-κB pathway.

Conclusion

These findings highlight the pathogenic role of IL-17 in Aβ-induced synaptic dysfunction and cognitive deficits. Inhibition of IL-17 could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulating the TRAF6/NF-κB pathway, which provides new clues for the mechanism of Aβ-induced cognitive impairments.
DnaK and DnaJ proteins from Hsp70/40 family are involved in Rubisco biosynthesis in Synechocystis sp. PCC6803 and sustain the enzyme assembly in a heterologous system
Authors: Rydzy Małgorzata , Kolesiński Piotr , Szczepaniak Andrzej , Grzyb Joanna
Published: February 2023

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the first step of carbon fixation performed by photosynthetic organisms. Form I of this enzyme found in plants and cyanobacteria is composed of eight large (RbcL) and eight small (RbcS) subunits. To form a functional enzyme, Rubisco subunits need to be properly folded, with the assistance of cellular chaperone machinery, and consecutively assembled in a strictly orchestrated manner, with the help of multiple auxiliary factors. In recent years, multiple Rubisco assembly chaperones and their function in enzyme biogenesis have been extensively characterized. Little is known about the potential specialized factors involved in Rubisco subunits folding at the pre-chaperonin stage, yet this knowledge is greatly needed for the fast and efficient testing of new Rubisco variants.

Synechococcussp. PCC 6803 Rubisco shows limited solubility and a lack of assembly in theEscherichia coliexpression system. In this study, we aim to identify which additional chaperones are necessary and sufficient in sustaining the heterologous assembly of native Rubisco. Our findings prove that upon the introduction ofSynechocystisDnaK2 to theE. colisystem, RbcL is produced in soluble form. The addition of specific DnaJ (Sll1384) enhances this effect. We explain these combined effects based on binding constancies, measured for particular partners in vitro, as well as our analysis of the putative tertiary structure of the proteins. Our results have potential implications for Rubisco engineering.
Power and sample sizes estimation in clinical trials with treatment switching in intention-to-treat analysis: a simulation study
Authors: Deng Lejun , Hsu Chih-Yuan , Shyr Yu
Published: February 2023

Background

Treatment switching, also called crossover, is common in clinical trials because of ethical concerns or other reasons. When it occurs and the primary objective is to identify treatment effects, the most widely used intention-to-treat analysis may lead to underpowered trials. Here, we presented an approach to preview power reductions and to estimate sample sizes required to achieve the desired power when treatment switching occurs in the intention-to-treat analysis.

Methods

We proposed a simulation-based approach and developed an R package to perform power and sample sizes estimation in clinical trials with treatment switching.

Results

We simulated a number of randomized trials incorporating treatment switching and investigated the impact of the relative effectiveness of the experimental treatment to the control, the switching probability, the switching time, and the deviation between the assumed and the real distributions for the survival time on power reductions and sample sizes estimation. The switching probability and the switching time are key determinants for significant power decreasing and thus sample sizes surging to maintain the desired power. The sample sizes required in randomized trials absence of treatment switching vary from around four-fifths to one-seventh of the sample sizes required in randomized trials allowing treatment switching as the switching probability increases. The power reductions and sample sizes increase with the decrease of switching time.

Conclusions

The simulation-based approach not only provides a preview for power declining but also calculates the required sample size to achieve an expected power in the intention-to-treat analysis when treatment switching occurs. It will provide researchers and clinicians with useful information before randomized controlled trials are conducted.
Different responses of Japanese encephalitis to weather variables among eight climate subtypes in Gansu, China, 2005–2019
Authors: Li Ruifen , Zhao Xiaohong , Tian Yu , Shi Yanjun , Gu Xueyan , Wang Shuang , Zhang Rui , An Jing , Su Li , Wang Xuxia
Published: February 2023

This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (β), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high–high clusters), α, β, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV’s distribution in Gansu Province are needed.
Peripheral immune cell profiling of double-hit lymphoma by mass cytometry
Authors: Lei Tao , Wu Gongqiang , Xu Yongjin , Zhuang Weihao , Lu Jialiang , Han Shuiyun , Zhuang Yuxin , Dong Xiaowu , Yang Haiyan
Published: February 2023

Background

Double-hit or Triple-hit lymphoma (DHL/THL) is a subset of high-grade B cell lymphoma harboring rearrangements ofMYCandBCL2and/orBCL6, and usually associate with aggressive profile, while current therapies tend to provide poor clinical outcomes and eventually relapsed. Further explorations of DHL at cellular and molecular levels are in demand to offer guidance for clinical activity.

Methods

We collected the peripheral blood of DHL patients and diffused large B cell lymphoma (DLBCL) patients from single institute and converted them into PBMC samples. Mass cytometry was then performed to characterize these samples by 42 antibody markers with samples of healthy people as control. We divided the immune cell subtypes based on the expression profile of surface antigens, and the proportion of each cell subtype was also analyzed. By comparing the data of the DLBCL group and the healthy group, we figured out the distinguished immune cell subtypes of DHL patients according to their abundance and marker expression level. We further analyzed the heterogeneity of DHL samples by pairwise comparison based on clinical characteristics.

Results

We found double-positive T cells (DPT) cells were in a significantly high percentage in DHL patients, whereas the ratio of double-negative T cells (DNT) was largely reduced in patients. Besides, CD38 was uniquely expressed at a high level on some naïve B cells of DHL patients, which could be a marker for the diagnosis of DHL (distinguishing from DLBCL), or even be a drug target for the treatment of DHL. In addition, we illustrated the heterogeneity of DHL patients in terms of immune cell landscape, and highlightedTP53as a major factor that contributes to the heterogeneity of the T cells profile.

Conclusion

Our study demonstrated the distinct peripheral immune cell profile of DHL patients by contrast to DLBCL patients and healthy people, as well as the heterogeneity within the DHL group, which could provide valuable guidance for the diagnosis and treatment of DHL.
First nosocomial infections in children supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO)
Authors: Cousin Vladimir L. , Rodriguez-Vigouroux Robert , Karam Oliver , Rimensberger Peter , Posfay-Barbe Klara M.
Published: February 2023

Background

Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a standard procedure for patient with refractory shock in Pediatric Intensive Care Unit (PICU). There is a paucity of data on the time relationship between VA-ECMO support, nosocomial infection occurrence, and PICU length of stay (LOS). The aim of this study was to determine the characteristics and impact of ECMO-related infections.

Methods

This is a retrospective study from 01/2008 to 12/2014, enrolling children with a VA-ECMO support for > 6 h. We recorded the first PICU infection during the VA-ECMO run, defined as a positive microbiological sample with clinical signs of infection or clinical signs of severe infection without positive sample.

Results

During the study period, 41 patients (25/41 male) were included, with a median age of 41.2 months (IQR 12.9–89.9) and a 53% mortality rate. Median time on VA-ECMO was 4.2 d (IQR 2–7.1), median PICU LOS was 14.7 d (IQR 4,7–26,9). Overall, 34% patients developed an infection, with an incidence of 60/1000 VA-ECMO days. Median time to first infection was 4 d (IQR 3–5), with Pseudomonas spp. being the most commonly detected microorganism (42%). Infected sites were ventilator-associated pneumonia (9/14), sternotomy infection (2/14), bloodstream (2/14) and urinary tract infections (1/14). Longer VA-ECMO support (> 5 d) (OR 5.9 (CI 95% 1.4–24.6; p = 0.01) and longer PICU stay (> 14 d) (OR 12 (95% CI 2.2–65.5; p = 0.004) were associated with infection.

Conclusion

In this single-center study, we underlined the high proportion and early occurrence of infections in patient on VA-ECMO, mostly in the first week. As infection was an early event, it may prolong the duration of VA-ECMO support and PICU LOS. Further research is needed to better understand the impact of infections on VA-ECMO and develop prevention strategies.
Feto-placental endothelial dysfunction in Gestational Diabetes Mellitus under dietary or insulin therapy
Authors: Wang Jing-Jing , Wang Xi , Li Qian , Huang Hua , Zheng Qiao-Ling , Yao Qin , Zhang Jun
Published: February 2023

Objective

Gestational diabetes mellitus (GDM) is a serious complication in pregnancy. Despite controlling the plasma glucose levels with dietary intervention (GDM-D) or insulin therapy (GDM-I), children born of diabetic mothers suffer more long-term complications from childhood to early adulthood. Placental circulation and nutrient exchange play a vital role in fetal development. Additionally, placental endothelial function is an indicator of vascular health, and plays an important role in maintaining placental circulation for nutrient exchange. This study was conducted to assess changes in fetal endothelial dysfunction in GDM under different interventions during pregnancy.

Methods

The primary human umbilical vein endothelial cells (HUVECs) were obtained from normal pregnant women (n = 11), GDM-D (n = 14), and GDM-I (n = 12) patients. LC-MS/MS was used to identify differentially expressed proteins in primary HUVECs among the three groups, after which Bioinformatics analysis was performed. Glucose uptake, ATP level, apoptosis, and differentially expressed proteins were assessed to investigate changes in energy metabolism.

Results

A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were identified after comparing patients with GDM-D/GDM-I and healthy controls. Of the 142, 64 proteins were upregulated while 77 were downregulated. Bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes and signaling pathways related to cellular processes, biological regulation, and metabolic processes. According to the results from KEGG analysis, there were changes in the PI3K/AKT signaling pathway after comparing the three groups. In addition, there was a decrease in glucose uptake in the GDM-I (P < 0.01) group. In GDM-I, there was a significant decrease in the levels of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3). Moreover, glucose uptake was significantly decreased in GDM-I, although in GDM-D, there was only a decrease in the levels of GLUT1. ATP levels decreased in GDM-I (P < 0.05) and apoptosis occurred in both the GDM-D and GDM-I groups. Compared to the normal controls, the levels of phosphate AKT and phosphate AMPK over total AKT and AMPK were reduced in the GDM-I group.

Conclusion

In summary, endothelial dysfunction occurred in pregnancies with GDM even though the plasma glucose levels were controlled, and this dysfunction might be related to the degree of glucose tolerance. The energy dysfunction might be related to the regulation of the AKT/AMPK/mTOR signaling pathway.
A novel ex vivo perfusion-based mandibular pig model for dental product testing and training
Authors: van Erk Machteld , Lomme Roger M. L. M. , Roozen Edwin A. , van Oirschot Bart A. J. A. , van Goor Harry
Published: February 2023

Background

A translational ex vivo perfusion-based mandibular pig model was developed as an alternative to animal experiments, for initial assessment of biomaterials in dental and maxillofacial surgery and training. This study aimed to assess the face and content validity of the novel perfusion-based model.

Methods

Cadaveric porcine heads were connected to an organ assist perfusion device for blood circulation and tissue oxygenation. Dental professionals and dental trainees performed a surgical procedure on the mandibula resembling a submandibular extraoral incision to create bone defects. The bone defects were filled and covered with a commercial barrier membrane. All participants completed a questionnaire using a 5-point Likert scale to assess the face and content validity of the model. Validation data between the two groups of participants were compared with Mann–Whitney U test.

Results

Ten dental professionals and seven trainees evaluated the model for face and content validity. Participants reported model realism, with a mean face validity score of 3.9 ± 1.0 and a content validity of 4.1 ± 0.8. No significant differences were found for overall face and content validity between experts and trainees.

Conclusion

We established face and content validity in a novel perfusion-based mandibular surgery model. This model can be used as an alternative for animal studies evaluating new biomaterials and related dental and maxillofacial surgical procedural training.
Risk of cardiometabolic outcomes among women with a history of pelvic inflammatory disease: a retrospective matched cohort study from the UK
Authors: Okoth Kelvin , Thomas G. Neil , Nirantharakumar Krishnarajah , Adderley Nicola J.
Published: February 2023

Introduction

To describe the incidence and prevalence of pelvic inflammatory disease (PID) and to estimate the risk of cardiometabolic outcomes among women with PID compared to women without PID.

Methods

A UK retrospective matched cohort study using data from The Health Improvement Network. To assess cardiometabolic risk, women (aged ≥ 16 years) with PID were compared to matched controls without PID. Annual prevalence and incidence of PID (1998–2017) were estimated among women aged 16–50 years using annual cross-sectional and cohort analyses, respectively. Adjusted hazard ratios (aHR) and 95% CI for cardiometabolic outcomes were estimated using Cox proportional hazards models. The primary outcome was composite cardiovascular disease (CVD) and its subtypes, including ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were hypertension, and type 2 diabetes mellitus (T2DM).

Results

Among the 715 recorded composite CVD events, the crude incidence rate per 1000 person-years was 1.5 among women with history of PID compared to 1.3 in matched controls. Compared to women without PID (N = 73,769), the aHRs for cardiometabolic outcomes among women with PID (N = 19,804) were: composite CVD 1.10 (95% CI 0.93–1.30); IHD 1.19 (95% CI 0.93–1.53); cerebrovascular disease 1.13 (95% CI 0.90–1.43); HF 0.92 (95% CI 0.62–1.35) hypertension 1.10 (95% CI 1.01–1.20); and T2DM 1.25 (95% CI 1.09–1.43). The prevalence (per 10,000 population) of PID was 396.5 in 1998 and 237 in 2017. The incidence (per 10,000 person-years) of PID was 32.4 in 1998 and 7.9 in 2017.

Conclusion

There was no excess risk of composite CVD or its subtypes among women with history of PID compared to matched controls. Findings from our study suggest that history of PID was associated with an increased risk of hypertension and type 2 diabetes mellitus, two major risk factors for CVD. Additional studies are required to support these findings.