bluuebunny/crossref_metadata_2025 huggingface dataset:
Vector-delivered artificial miRNA effectively inhibits Porcine epidemic diarrhea virus replication
Authors: Zhu Tingfan , Qian Jinhan , Shen Zijun , Shao Hongxia , Qian Kun , Jin Wenjie , Qin Aijian
Published: July 2023

Background

Porcine epidemic diarrhea virus (PEDV) is an α-coronavirus that causes highly contagious intestinal infectious disease, involving clinically characterized by diarrhea, dehydration, vomiting, and high mortality to suckling piglets. As a strategy for antiviral therapy, artificial microRNA (amiRNA) mediated suppression of viral replication has recently become increasingly important. In this study, we evaluated the advantages of using an amiRNA vector against PEDV.

Methods

In this study, we evaluated the advantages of using an amiRNA vector against PEDV. We designed two single amiRNA sequences for different conserved sequences of the PEDV S and N genes, and tested their inhibitory effects on PEDV in Vero cells.

Results

It was obvious from the CCK-8 results that the transient transfection of amiRNA was non-toxic to the cells. In addition, our results showed that the transient expression of two amiRNAs (amiRNA-349 and amiRNA-1447) significantly reduced the expression of viral RNA and protein in the cells. The TCID50 results showed that the release of virus particles into the culture supernatant was significantly reduced, with an effect as high as 90%. To avoid virus mutation escape, the above two single amiRNA sequences were tandem in this study (amiRNA-349 + 1447), enabling a single microRNA to be expressed simultaneously. The real-time PCR and Western blot results showed that the inhibitory effect was significantly enhanced in each of the different time periods. The TCID50 results showed that the release of virus particles in the culture supernatant was significantly reduced at the different time periods.

Conclusions

In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.
Locality-sensitive bucketing functions for the edit distance
Authors: Chen Ke , Shao Mingfu
Published: July 2023

Background

Many bioinformatics applications involve bucketing a set of sequences where each sequence is allowed to be assigned into multiple buckets. To achieve both high sensitivity and precision, bucketing methods are desired to assign similar sequences into the same bucket while assigning dissimilar sequences into distinct buckets. Existingk-mer-based bucketing methods have been efficient in processing sequencing data with low error rates, but encounter much reduced sensitivity on data with high error rates. Locality-sensitive hashing (LSH) schemes are able to mitigate this issue through tolerating the edits in similar sequences, but state-of-the-art methods still have large gaps.

Results

In this paper, we generalize the LSH function by allowing it to hash one sequence into multiple buckets. Formally, a bucketing function, which maps a sequence (of fixed length) into a subset of buckets, is defined to be$$(d_1, d_2)$$(d1,d2)-sensitive if any two sequences within an edit distance of$$d_1$$d1are mapped into at least one shared bucket, and any two sequences with distance at least$$d_2$$d2are mapped into disjoint subsets of buckets. We construct locality-sensitive bucketing (LSB) functions with a variety of values of$$(d_1,d_2)$$(d1,d2)and analyze their efficiency with respect to the total number of buckets needed as well as the number of buckets that a specific sequence is mapped to. We also prove lower bounds of these two parameters in different settings and show that some of our constructed LSB functions are optimal.

Conclusion

These results lay the theoretical foundations for their practical use in analyzing sequences with high error rates while also providing insights for the hardness of designing ungapped LSH functions.
Radiological evidence of rapid growth acceleration of a small part solid nodule found to be large-cell carcinoma of the lung
Authors: Lu Yunwei , Sun Zewen , Li Hao , Chen Xiaofeng , Li Yun , Sun Lina , Yang Fan , Jiang Guanchao , Zhou Jian
Published: July 2023

Background

With the widespread use of low-dose computed tomography for lung cancer screening, the detection rate of pulmonary lesions manifesting as ground-glass opacities (GGOs) has been increasing dramatically. The volume doubling time (VDT) has been introduced in clinical practice to monitor the potential growth rate of GGOs during long-term follow-up periods.

Case presentation

A 72-year-old never-smoker female diagnosed with mixed GGO manifested abruptly accelerated growth with sudden decreased VDT from 400 to 36 days. A thoracoscopic left lower lobectomy with mediastinal lymph node dissection was performed, and the diagnosis was stage IB large-cell neuroendocrine carcinoma (LCNEC). Next-generation sequencing of the tumor highlights an EML4-ALK gene fusion.

Conclusions

The LCNEC may present as GGO with longer VDT in the early stage. VDT should calculate by the whole size either on the entire tumor diameter or on consolidation diameter. It is recommended that meticulous long-term follow-up with dynamic VDT monitoring may help select high-risk GGOs performing timely semi-elective surgical resection in clinical practice.
C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity
Authors: Aimi Takahiro , Matsuda Keiko , Yuzaki Michisuke
Published: July 2023

Changes in neural activity induced by learning and novel environments have been reported to lead to the formation of new synapses in the adult brain. However, the underlying molecular mechanism is not well understood. Here, we show that Purkinje cells (PCs), which have established adult-type monosynaptic innervation by climbing fibers (CFs) after elimination of weak CFs during development, can be reinnervated by multiple CFs by increased expression of the synaptic organizer C1ql1 in CFs or Bai3, a receptor for C1ql1, in PCs. In the adult cerebellum, CFs are known to have transverse branches that run in a mediolateral direction without forming synapses with PCs. Electrophysiological, Ca2+-imaging and immunohistochemical studies showed that overexpression of C1ql1 or Bai3 caused these CF transverse branches to elongate and synapse on the distal dendrites of mature PCs. Mature PCs were also reinnervated by multiple CFs when the glutamate receptor GluD2, which is essential for the maintenance of synapses between granule cells and PCs, was deleted. Interestingly, the effect of GluD2 knockout was not observed in Bai3 knockout PCs. In addition, C1ql1 levels were significantly upregulated in CFs of GluD2 knockout mice, suggesting that endogenous, not overexpressed, C1ql1-Bai3 signaling could regulate the reinnervation of mature PCs by CFs. Furthermore, the effects of C1ql1 and Bai3 overexpression required neuronal activity in the PC and CF, respectively. C1ql1 immunoreactivity at CF-PC synapses was reduced when the neuronal activity of CFs was suppressed. These results suggest that C1ql1-Bai3 signaling may mediate CF synaptogenesis in mature PCs, potentially in concert with neuronal activity.
Exploring association of melanoma-specific Bcl-xL with tumor immune microenvironment
Authors: Lucianò Anna Maria , Di Martile Marta , Pérez-Oliva Ana B. , Di Caprio Marica , Foddai Maria Laura , Buglioni Simonetta , Mulero Victoriano , Del Bufalo Donatella
Published: July 2023

Background

Macrophages take center stage in the tumor microenvironment, a niche composed of extracellular matrix and a heterogeneous group of cells, including immune ones. They can evolve during tumor progression and acquire Tumor-Associated Macrophage (TAMs) phenotype. The release of cytokines by tumor and stromal cells, influence the secretion of cytokines by TAMs, which can guarantee tumor progression and influence the response to therapy. Among all factors able to recruit and polarize macrophages, we focused our attention on Bcl-xL, a multifaceted member of the Bcl-2 family, whose expression is deregulated in melanoma. It acts not only as a canonical pro-survival and anti-apoptotic protein, but also as a promoter of tumor progression.

Methods

Human melanoma cells silencing or overexpressing Bcl-xL protein, THP-1 monocytic cells and monocyte-derived macrophages were used in this study. Protein array and specific neutralizing antibodies were used to analyze cytokines and chemokines secreted by melanoma cells. qRT-PCR, ELISA and Western Blot analyses were used to evaluate macrophage polarization markers and protein expression levels. Transwell chambers were used to evaluate migration of THP-1 and monocyte-derived macrophages. Mouse and zebrafish models were used to evaluate the ability of melanoma cells to recruit and polarize macrophages in vivo.

Results

We demonstrated that melanoma cells overexpressing Bcl-xL recruit macrophages at the tumor site and induce a M2 phenotype. In addition, we identified that interleukin-8 and interleukin-1β cytokines are involved in macrophage polarization, and the chemokine CCL5/RANTES in the macrophages recruitment at the tumor site. We also found that all these Bcl-xL-induced factors are regulated in a NF-kB dependent manner in human and zebrafish melanoma models.

Conclusions

Our findings confirmed the pro-tumoral function of Bcl-xL in melanoma through its effects on macrophage phenotype.
The impact of a blend of Pistacia atlantica seed and canola oil compared with a blend of corn-canola oil with synthetic antioxidant and corn-canola oil without synthetic antioxidant on oxidative stress markers in patients with metabolic syndrome: protocol for a triple-blind, randomized, three-way cross-over clinical trial
Authors: Sasanfar Bahareh , Emrani Arezoo sadat , Zademohammadi Faezeh , Forootani Bita , Emamgholipour Solaleh , Jambarsang Sara , Khayyatzadeh Sayyed Saeid , Pourrajab Fatemeh , Yasini Ardakani Seyed Ali , Esmaillzadeh Ahmad , Salehi-Abarghouei Amin
Published: July 2023

Background

Metabolic syndrome (MetS) is regarded as a complex metabolic disorder. Recently, the role of dietary antioxidants in the underlying pathogenesis and complications of MetS has come into focus. Pistacia atlantica oil is known as a high antioxidant oil which might improve the antioxidant status of dietary oils and also oxidative stress markers. On the other hand, tert-Butylhydroquinone (TBHQ) is an approved food-grade synthetic antioxidant that acts both as an inducer and inhibitor of carcinogenesis. The current trial will explore the possible effect of a blend of Pistacia atlantica seed-canola oils, corn-canola oils with TBHQ, and corn-canola oil without TBHQ on oxidative stress markers in patients with MetS.

Methods

We will conduct a single-center, triple-blind, three-way randomized cross-over clinical trial (RCT) among 72 patients with MetS. After a 1-month run-in period, eligible participants will consume the intervention oils as their regularly consumed oils in a random order. Each intervention period will last 8 weeks separated by 4-week washout periods. Anthropometric indices, body composition, physical activity, blood pressure, and 24-h dietary food recall measurements will be assessed at the beginning and the end of each intervention period. The primary outcome will be oxidative stress markers including serum total antioxidant capacity, total oxidant status, malondialdehyde, nitric oxide, and the enzyme activity of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The secondary outcomes will be changes in MetS components including blood pressure, fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, and anthropometric measurements.

Discussion

Pistacia atlantica seed oil is high in antioxidants. An intervention with this oil could offer an option for oxidative stress prevention among patients with metabolic syndrome. The present clinical trial will be the first one assessing the impact of Pistacia atlantica oil on human oxidative stress markers.

Trial registration

Iranian Registry of Clinical trials IRCT20130223012571N8. Registered on 4 March 2022.
The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT)
Authors: Simoes Jorge Piano , Schoisswohl Stefan , Schlee Winfried , Basso Laura , Bernal-Robledano Alberto , Boecking Benjamin , Cima Rilana , Denys Sam , Engelke Milena , Escalera-Balsera Alba , Gallego-Martinez Alvaro , Gallus Silvano , Kikidis Dimitris , López-Escámez Jose A. , Marcrum Steven C. , Markatos Nikolaos , Martin-Lagos Juan , Martinez-Martinez Marta , Mazurek Birgit , Vassou Evgenia , Jarach Carlotta Micaela , Mueller-Locatelli Nicolas , Neff Patrick , Niemann Uli , Omar Hafez Kader , Puga Clara , Schleicher Miro , Unnikrishnan Vishnu , Perez-Carpena Patricia , Pryss Rüdiger , Robles-Bolivar Paula , Rose Matthias , Schecklmann Martin , Schiele Tabea , Schobel Johannes , Spiliopoulou Myra , Stark Sabine , Vogel Carsten , Wunder Nina , Zachou Zoi , Langguth Berthold
Published: July 2023

Background

Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient.

Methods

Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT.

Discussion

The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results.

Trial registration

ClinicalTrials.gov NCT04663828. The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.
Assisted ambulation to improve health outcomes for older medical inpatients (AMBULATE): study protocol for a randomized controlled trial
Authors: Johnson Joshua K. , Hamilton Aaron C. , Hu Bo , Pack Quinn R. , Lindenauer Peter K. , Fox Robert J. , Hashmi Ardeshir , Siegmund Lee Anne , Burchill Christian N. , Taksler Glen B. , Goto Toyomi , Stilphen Mary , Rothberg Michael B.
Published: July 2023

Background

Hospitalized older adults spend as much as 95% of their time in bed, which can result in adverse events and delay recovery while increasing costs. Observational studies have shown that general mobility interventions (e.g., ambulation) can mitigate adverse events and improve patients’ functional status. Mobility technicians (MTs) may address the need for patients to engage in mobility interventions without overburdening nurses. There is no data, however, on the effect of MT-assisted ambulation on adverse events or functional status, or on the cost tradeoffs if a MT were employed. The AMBULATE study aims to determine whether MT-assisted ambulation improves mobility status and decreases adverse events for older medical inpatients. It will also include analyses to identify the patients that benefit most from MT-assisted mobility and assess the cost-effectiveness of employing a MT.

Methods

The AMBULATE study is a multicenter, single-blind, parallel control design, individual-level randomized trial. It will include patients admitted to a medical service in five hospitals in two regions of the USA. Patients over age 65 with mild functional deficits will be randomized using a block randomization scheme. Those in the intervention group will ambulate with the MT up to three times daily, guided by the Johns Hopkins Mobility Goal Calculator. The intervention will conclude at hospital discharge, or after 10 days if the hospitalization is prolonged. The primary outcome is the Short Physical Performance Battery score at discharge. Secondary outcomes are discharge disposition, length of stay, hospital-acquired complications (falls, venous thromboembolism, pressure ulcers, and hospital-acquired pneumonia), and post-hospital functional status.

Discussion

While functional decline in the hospital is multifactorial, ambulation is a modifiable factor for many patients. The AMBULATE study will be the largest randomized controlled trial to test the clinical effects of dedicating a single care team member to facilitating mobility for older hospitalized patients. It will also provide a useful estimation of cost implications to help hospital administrators assess the feasibility and utility of employing MTs.

Trial registration

Registered in the United States National Library of Medicine clinicaltrials.gov (# NCT05725928). February 13, 2023.
The probability distributions of the movement of dairy and beef cattle in Japan: a data note
Authors: Murato Yoshinori , Hayama Yoko , Kondo Sonoko , Sawai Kotaro , Yamaguchi Emi , Yamamoto Takehisa
Published: July 2023

Objectives

Animal movement is an important factor in the transmission of infectious diseases among livestock. A better understanding of animal movement characteristics provides a more reliable estimation of disease spread and promotes modeling studies. In Japan, all the cattle movement information is recorded in a national database called the Individual Cattle Identification Register (ICIR).” Our previous studies using this information demonstrated heterogeneity in the movement of dairy and beef cows according to location, season, and age. The present study describes the probability distributions of the movement of Japanese dairy and beef cows in the following month on a regional basis.

Data description

This publication contains four probability distribution datasets for the predicted locations of dairy and beef cows in Japan in the following month, which were developed using individual cattle movement information obtained from the ICIR. These datasets provide information on cattle movement in the following month on a regional basis, given properties such as birth region, location, time, and age.
Obstructive lithiasis of the lower bile duct discovered four decades after cholecystectomy and its management by ideal choledochotomy: a case report
Authors: Kamla Joël Igor , Bang Guy Aristide , Tochie Joel Noutakdie , Tchuenkam Landry Wakheu , Essomba Arthur Georges
Published: July 2023

Background

Residual lithiasis is the presence of stones in the common bile duct, ignored after one or more biliary interventions. We report an atypical case of chronic symptomatic lithiasis of the lower bile duct occurring 41 years after biliary surgery, managed successfully by ideal choledochotomy.

Case presentation

A 68-year-old Black African female with several past laparotomies including a cholecystectomy forty-one years ago presented with hepatic colic-type pain that had been intermittent for several years but worsened recently. Her clinical, biological, and imaging test assessments were suggestive of a residual obstructive lithiasis of the lower common bile duct. Through an open right subcostal laparotomy approach, a dilated bile duct of approximately 3 cm was found and managed by transverse choledochotomy in which the stone was extracted in retrograde manner. After confirmation of disobstruction, a primitive bile duct suture without biliary drainage was performed and a tubular drain was positioned under the liver. The postoperative course was uneventful at follow-up of 30 days.

Conclusion

Residual choledocholithiasis can be avoided. We performed an ideal choledochotomy, of which the follow-up was simple.
Dendritic cells mediated by small extracellular vesicles derived from MSCs attenuated the ILC2 activity via PGE2 in patients with allergic rhinitis
Authors: Liu Xiao-Qing , Peng Ya-Qi , Huang Long-Xin , Li Chan-Gu , Kuang Peng-Peng , Chen De-Hua , Wu Zi-Cong , He Bi-Xin , Zhou Zhi-Rou , Fu Qing-Ling
Published: July 2023

Background

Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs.

Methods

Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems.

Results

sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs.

Conclusions

We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.
Animal behaviour on the move: the use of auxiliary information and semi-supervision to improve behavioural inferences from Hidden Markov Models applied to GPS tracking datasets
Authors: Saldanha Sarah , Cox Sam L. , Militão Teresa , González-Solís Jacob
Published: July 2023

Background

State-space models, such as Hidden Markov Models (HMMs), are increasingly used to classify animal tracks into behavioural states. Typically, step length and turning angles of successive locations are used to infer where and when an animal is resting, foraging, or travelling. However, the accuracy of behavioural classifications is seldom validated, which may badly contaminate posterior analyses. In general, models appear to efficiently infer behaviour in species with discrete foraging and travelling areas, but classification is challenging for species foraging opportunistically across homogenous environments, such as tropical seas. Here, we use a subset of GPS loggers deployed simultaneously with wet-dry data from geolocators, activity measurements from accelerometers, and dive events from Time Depth Recorders (TDR), to improve the classification of HMMs of a large GPS tracking dataset (478 deployments) of red-billed tropicbirds (Phaethon aethereus), a poorly studied pantropical seabird.

Methods

We classified a subset of fixes as either resting, foraging or travelling based on the three auxiliary sensors and evaluated the increase in overall accuracy, sensitivity (true positive rate), specificity (true negative rate) and precision (positive predictive value) of the models in relation to the increasing inclusion of fixes with known behaviours.

Results

We demonstrate that even with a small informed sub-dataset (representing only 9% of the full dataset), we can significantly improve the overall behavioural classification of these models, increasing model accuracy from 0.77 ± 0.01 to 0.85 ± 0.01 (mean ± sd). Despite overall improvements, the sensitivity and precision of foraging behaviour remained low (reaching 0.37 ± 0.06, and 0.06 ± 0.01, respectively).

Conclusions

This study demonstrates that the use of a small subset of auxiliary data with known behaviours can both validate and notably improve behavioural classifications of state space models of opportunistic foragers. However, the improvement is state-dependant and caution should be taken when interpreting inferences of foraging behaviour from GPS data in species foraging on the go across homogenous environments.
Combining cognitive theory and data driven approaches to examine students’ search behaviors in simulated digital environments
Authors: Tenison Caitlin , Sparks Jesse R.
Published: July 2023

Background

Digital Information Literacy (DIL) refers to the ability to obtain, understand, evaluate, and use information in digital contexts. To accurately capture various dimensions of DIL, assessment designers have increasingly looked toward complex, interactive simulation-based environments that afford more authentic learner performances. These rich assessment environments can capture process data produced by students’ goal driven interactions with digital sources but linking this data to inferences about the target constructs introduces significant measurement challenges which cognitive theory can help us address.

Methods

In this paper, we analyzed data generated from a simulated web search tool embedded within a theoretically-grounded virtual world assessment of multiple-source inquiry skills. We describe a multi-step clustering approach to identify patterns in student’s search processes by bringing together theory-informed process data indicators and sequence clustering methods.

Results

We identified four distinct search behaviors captured in students’ process data. We found that these search behaviors differed both in their contribution to the web search tool subscores as well as correlations with task level multiple-source inquiry subconstructs such as locating, evaluating, and synthesizing information. We argue that the search behaviors reflect differences in how students generate and update their task goals.

Conclusion

The data-driven approach we describe affords a qualitative understanding of student strategy use in a complex, dynamic simulation- and scenario-based environment. We discuss some of the strengths and challenges of using a theoretical understanding of multiple-source inquiry to inform how we processed, analyzed, and interpreted the data produced from this assessment tool and the implications of this approach for future research and development.
Awareness routing algorithm in vehicular ad-hoc networks (VANETs)
Authors: choudhary Deepak , Pahuja Roop
Published: July 2023

The behavior of a Vehicle Ad hoc Network (VANETs) is extremely unpredictable due to the high mobility and random network topology inherent to the nature of VANETs. Several problems, including frequent connection failures, scalability, multi-hop data transfer, and data loss, impact the performance of Transmission Control Protocols (TCP) in such wireless ad hoc networks. This study proposes using zone-based routing with consideration for mobility in VANETs as a means of avoiding this issue. A hybrid optimization approach is introduced and used to the routing process. Both Ant Colony Optimization (ACO) and Artificial Bee Colony Optimization (ABCO) are components of the hybrid algorithm (ABC). Link stability and Residual energy provide the basis of the fitness function. Several measures, including delivery ratio, time, and overhead, are used to evaluate the effectiveness of the suggested method. A comparison of the suggested method's efficiency with that of other algorithms.
The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma
Authors: Hayakawa Mineji , Tagami Takashi , Kudo Daisuke , Ono Kota , Aoki Makoto , Endo Akira , Yumoto Tetsuya , Matsumura Yosuke , Irino Shiho , Sekine Kazuhiko , Ushio Noritaka , Ogura Takayuki , Nachi Sho , Irie Yuhei , Hayakawa Katsura , Ito Yusuke , Okishio Yuko , Muronoi Tomohiro , Kosaki Yoshinori , Ito Kaori , Nakatsutsumi Keita , Kondo Yutaka , Ueda Taichiro , Fukuma Hiroshi , Saisaka Yuichi , Tominaga Naoki , Kurita Takeo , Nakayama Fumihiko , Shibata Tomotaka , Kushimoto Shigeki
Published: July 2023

Background

The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase.

Methods

This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7–9 or 10–12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%.

Results

The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49–2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days.

Conclusions

Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume.

Trial registration number:umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.
Adverse childhood experiences, child behavioral health needs, and family characteristics associated with the presence of a firearm in the home: a survey of parents in Chicago
Authors: Attridge Megan M. , Heffernan Marie E. , Bendelow Anne , Menker Carly G. , Davis Matthew M. , Sheehan Karen
Published: July 2023

Background

Firearm violence is the leading cause of pediatric mortality in the USA. The presence of a firearm in the home poses an immense risk to children with increased rates of suicide and unintentional injury by firearm. Recent literature has not explored child ACEs and child behavioral health needs with the presence of a firearm in the home. The objective of this study was to explore an association between these factors, parent health, family experience with firearm violence, and demographics, and the presence of a firearm in the home.

Results

Overall, 382 of 1,436 (weighted to 22.0%) responding parents reported the presence of a firearm in the home. In an adjusted model, the odds ratio of firearm presence increased incrementally with a child’s increasing exposure to ACEs. Compared to a child in the household exposed to no ACEs, a child in the household exposed to two or more ACEs was associated with a 5.16 times higher odds of firearm presence in the home (95% confidence interval (CI) 2.92–9.10). Similarly, a child in the household who had used behavioral health services was associated with a 2.10 times higher odds of firearm presence in the home (95% CI 1.35–3.26), compared to a child in the household who had not. Presence of firearm in the home was also associated with higher household income, younger parent age (under 35 years), and male parent gender.

Conclusions

Chicago parents have higher odds of reporting the presence of a firearm in the home when living in a household with a child exposed to ACEs and with behavioral health needs. These findings could inform future public health interventions and targeted safe storage messaging to prevent pediatric firearm injury in the home.
An MRI-based radiomics nomogram for differentiating spinal metastases from multiple myeloma
Authors: Zhang Shuai , Liu Menghan , Li Sha , Cui Jingjing , Zhang Guang , Wang Ximing
Published: July 2023

Background

Spinal metastasis and multiple myeloma share many overlapping conventional radiographic imaging characteristics, thus, their differentiation may be challenging. The purpose of this study was to develop and validate an MRI-based radiomics nomogram for the differentiation of spinal metastasis and multiple myeloma.

Materials and methods

A total of 312 patients (training set: n = 146, validation set: n = 65, our center; external test set: n = 101, two other centers) with spinal metastasis (n = 196) and multiple myeloma (n = 116) were retrospectively enrolled. Demographics and MRI findings were assessed to build a clinical factor model. Radiomics features were extracted from MRI images. A radiomics model was constructed by the least absolute shrinkage and selection operator method. A radiomics nomogram combining the radiomics signature and independent clinical factors was constructed. And, one experienced radiologist reviewed the MRI images for all case. The diagnostic performance of the different models was evaluated by receiver operating characteristic curves.

Results

A clinical factors model was built based on heterogeneous appearance and shape. Twenty-one features were used to build the radiomics signature. The area under the curve (AUC) values of the radiomics nomogram (0.853 and 0.762, respectively) were significantly higher than that of the clinical factor model (0.692 and 0.540, respectively) in both validation (p = 0.048) and external test (p < 0.001) sets. The AUC values of the radiomics nomogram model were higher than that of radiologist in training, validation and external test sets (all p < 0.05). Moreover, no significant difference in AUC values of radiomics nomogram model was found between the validation set and external test set (p = 0.212).

Conclusion

The radiomics nomogram can differentiate spinal metastasis and multiple myeloma with a moderate to good performance, and may be as a valuable method to assist in the clinical diagnosis and preoperative decision-making.
Differences in foot shape when wearing wedge-heeled shoes with elevated forefoot height and heel height
Authors: Zhu Ao , Lee Yu-Chi
Published: July 2023

Wedge-heeled shoes, which are formed by elevating both the forefoot and heel, have been popular among young women. However, research on the foot shape in wedge-heeled shoes is lacking. This study aimed to access the effects of forefoot height (10, 20, and 30 mm) and heel height (30, 50, 70, and 90 mm) on foot shape and perceived comfort when wearing wedge-heeled shoes. Three-dimensional (3D) foot scanning was performed on 35 females and the 14 foot dimensions were measured. Increased forefoot height generated larger lengths (foot, ball and out ball), smaller girths (ball and instep) and heights (instep and navicular) (p < 0.05). Thus, when the forefoot height increased, the foot became longer, slimmer and flatter. Moreover, elevated heel height resulted in larger dimensions for girths (ball and instep), heights (instep and navicular), and smaller dimensions for lengths (foot, ball and out ball), widths (diagonal and horizontal) and toe 5 angles of the foot (p < 0.01). That means shorter, narrower and more convex foot shapes were observed when heel height increased. Subjective measurements implied that increased forefoot height significantly enhanced perceived comfort, whereas increased heel height diminished comfort. It was found that forefoot elevation could result in less deformation and discomfort which accompanied heel elevation, especially in the low heel-toe drop combinations (10 × 30 and 20 × 30 mm). The findings provide valuable references for enhancing shoe fitting and comfort for wedge-heeled shoes by providing dimensional data on the toe, ball, arch and instep regions.
Mechanical insufflation-exsufflation to promote extubation success in critically ill adults on intensive care: protocol for a randomised controlled feasibility trial
Authors: Swingwood Ema , Voss Sarah , Tume Lyvonne N. , Bewley Jeremy , Turner Nicholas , Ntoumenopoulos George , Rose Louise , Cramp Fiona
Published: July 2023

Background

Extubation failure, defined as reintubation within 48 h, is associated with increased intensive care unit (ICU) length of stay and higher mortality risk. One cause of extubation failure is secretion retention, resulting from an inability to cough effectively. Mechanical insufflation-exsufflation (MI-E) simulates a cough aiding secretion clearance. However, MI-E is not routinely used in the ICU for invasively ventilated patients. This study aims to determine feasibility and acceptability of a randomised controlled trial (RCT) examining MI-E use to promote extubation success in intubated, ventilated adults.

Methods

It is a single-centre, feasibility RCT with semi-structured interviews, economic scoping, and exploratory physiology study.

The feasibility RCT (n = 50) will compare standard care to a MI-E protocol including a minimum of two MI-E sessions via the endotracheal tube prior to extubation. Post-extubation, MI-E will be delivered via facemask or mouthpiece up to two times/day for 48 h. MI-E settings will be individualised. All patients will receive standard care (no MI-E) in relation to mechanical ventilation, weaning, rehabilitation, physiotherapy techniques such as positioning, manual airway clearance techniques, manual/ventilator hyperinflation, endotracheal suctioning, and nebulisation. Clinical data collection will occur before, on completion, and 5-min post-physiotherapy sessions (intervention/control arms). Resource use will be calculated for each 24-h period. Analyses will be descriptive and address feasibility outcomes including participant recruitment and attrition, proportion of MI-E treatment sessions completed, dataset completeness, and frequency of adverse events and acceptability.

Semi-structured online interviews informed by the Theoretical Framework of Acceptability (TFA) with patients, clinicians, and family members will explore the acceptability of the MI-E intervention and study processes.

Interview data will be analysed using reflexive thematic analysis based on TFA domains through first-level coding.

The embedded physiology study will use electrical impedance tomography and lung ultrasound to explore lung recruitment and de-recruitment during MI-E in a subset of 5–10 patients.

Discussion

This study will examine feasibility and acceptability of a RCT protocol of MI-E to promote extubation success. Study findings will inform design modification and conduct of a future adequately powered trial. Furthermore, the study will contribute and advance the understanding of MI-E use in critically ill intubated adults.

Trial registration

ISRCTN 24603037; IRAS 303674
Prevalence of overweight and obesity among Iranian population: a systematic review and meta-analysis
Authors: Abiri Behnaz , Ahmadi Amirhossein Ramezani , Amini Shirin , Akbari Mojtaba , Hosseinpanah Farhad , Madinehzad Seyed Ataollah , Hejazi Mahdi , Rishehri Amirreza Pouladi , Naserghandi Alvand , Valizadeh Majid
Published: July 2023

Background

Obesity is a major risk factor for chronic diseases. Politicians and practitioners should be aware of the dramatic increase in obesity and its subsequent complications to prevent associated health risks. This systematic review aimed to provide better insight into the prevalence of overweight and obesity in the Iranian population.

Method

An evaluation was conducted on all published observational studies from both national (SID, Irandoc, Iranmedex) and international (Web of Knowledge, PubMed, Scopus) sources, which reported the prevalence of overweight/obesity among normal population samples, between January 2012 and December 2021.

Result

A total of 152 eligible studies were included in this meta-analysis. Of the 152 selected studies, 74 reported the prevalence of overweight/obesity in patients aged ≤ 18 years, and 61 studies in adults. In the rest of the articles (17 studies), the results were reported for a combination of these age groups. The prevalence of overweight and obesity in Iran was estimated at 20.1 (95% CI 17.92–22.30) and 13.44 (95% CI 11.76–15.22), respectively. This percentage (95% CI) was 11.71 (10.98–12.46) for overweight and 8.08 (7.02–9.22) for obesity in those aged ≤ 18 years, and 35.26 (32.61–37.99) for overweight and 21.38 (19.61–23.20) for obesity in those aged > 18 years. The overall prevalence of overweight and obesity in the entire population was 35.09% (95% CI 31.31–38.98).

Conclusion

As obesity is on the rise in Iran, we should seek both weight loss strategies and ways to control comorbidities associated with high BMI.
Association between serum iron and liver transaminases based on a large adult women population
Authors: He Andong , Zhou Zhuoping , Huang Lili , Yip Ka Cheuk , Chen Jing , Yan Ruiling , Li Ruiman
Published: July 2023

Background

Studies are being focused on the potential roles of iron in various diseases, but remain unclear for the association between serum iron and liver injury, especially in adult women.

Methods

Based on the National Health and Nutrition Examination Survey, we investigated the relationship between serum iron and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among 19,185 adult women.

Results

Using weighted multivariate regression analyses, subgroup analyses, and threshold effect analyses, we found that serum iron was independently and positively correlated with ALT and AST. These associations differed in various age or race. Additionally, we found turning points in the curves of the relationship between serum iron and ALT in all women and the non-pregnant women. Using sensitivity analyses, we further found that the associations between serum iron and the liver transaminases remained positive in the non-pregnant women after adjusting for various covariates, but not in pregnant women. Besides, the positive associations between them kept present after excluding the women with high blood pressure, diabetes, and chronic kidney disease.

Conclusion

The present study indicated a positive association between serum iron and liver transaminases, indicating that serum iron may be a potential biomarker of liver function.
Molecular Tumor Board as a Clinical Tool for Converting Molecular Data Into Real-World Patient Care
Authors: Vingiani Andrea , Agnelli Luca , Duca Matteo , Lorenzini Daniele , Damian Silvia , Proto Claudia , Niger Monica , Nichetti Federico , Tamborini Elena , Perrone Federica , Piccolo Alberta , Manoukian Siranoush , Azzollini Jacopo , Brambilla Marta , Colombo Elena , Lopez Salvatore , Vernieri Claudio , Marra Francesca , Conca Elena , Busico Adele , Capone Iolanda , Bozzi Fabio , Angelini Marta , Devecchi Andrea , Salvatori Rebecca , De Micheli Valentina , Baggi Anna , Pasini Silvia , Jommi Claudio , Ladisa Vito , Apolone Giovanni , De Braud Filippo , Pruneri Giancarlo
Published: July 2023

PURPOSE

The investigation of multiple molecular targets with next-generation sequencing (NGS) has entered clinical practice in oncology, yielding to a paradigm shift from the histology-centric approach to the mutational model for personalized treatment. Accordingly, most of the drugs recently approved in oncology are coupled to specific biomarkers. One potential tool for implementing the mutational model of precision oncology in daily practice is represented by the Molecular Tumor Board (MTB), a multidisciplinary team whereby molecular pathologists, biologists, bioinformaticians, geneticists, medical oncologists, and pharmacists cooperate to generate, interpret, and match molecular data with personalized treatments.

PATIENTS AND METHODS

Since May 2020, the institutional MTB set at Fondazione IRCCS Istituto Nazionale Tumori of Milan met weekly via teleconference to discuss molecular data and potential therapeutic options for patients with advanced/metastatic solid tumors.

RESULTS

Up to October 2021, among 1,996 patients evaluated, we identified >10,000 variants, 43.2% of which were functionally relevant (pathogenic or likely pathogenic). On the basis of functionally relevant variants, 711 patients (35.6%) were potentially eligible to targeted therapy according to European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets tiers, and 9.4% received a personalized treatment. Overall, larger NGS panels (containing >50 genes) significantly outperformed small panels (up to 50 genes) in detecting actionable gene targets across different tumor types.

CONCLUSION

Our real-world data provide evidence that MTB is a valuable tool for matching NGS data with targeted treatments, eventually implementing precision oncology in clinical practice.
MiR-143 Targets SYK to Regulate NEFA Uptake and Contribute to Thermogenesis in Male Mice
Authors: Liu Jie , Wei Limin , Chen Ting , Wang Huan , Luo Junyi , Chen Xingping , Jiang Qingyan , Xi Qianyun , Sun Jiajie , Zhang Lin , Zhang Yongliang
Published: July 2023

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) and white adipose tissue (WAT) thermogenesis has emerged as an attractive tool for antiobesity. Although miR-143 has been reported to be associated with BAT thermogenesis, its role remains unclear. Here, we found that miR-143 had highest expression in adipose tissue, especially in BAT. During short-term cold exposure or CL316,243 was injected, miR-143 was markedly downregulated in BAT and subcutaneous WAT (scWAT). Moreover, knockout (KO) of miR-143 increases the body temperature of mice upon cold exposure, which may be due to the increased thermogenesis of BAT and scWAT. More importantly, supplementation of miR-143 in BAT of KO mice can inhibit the increase in body temperature in KO mice. Mechanistically, spleen tyrosine kinase was revealed for the first time as a new target of miR-143, and deletion of miR-143 facilitates fatty acid uptake in BAT. In addition, we found that brown adipocytes can promote fat mobilization of white adipocytes, and miR-143 may participate in this process. Meanwhile, we demonstrate that inactivation of adenylate cyclase 9 (AC9) in BAT inhibits thermogenesis through AC9–PKA–AMPK–CREB–UCP1 signaling pathway. Overall, our results reveal a novel function of miR-143 on thermogenesis, and a new functional link of the BAT and WAT.