bluuebunny/crossref_metadata_2025 huggingface dataset:
Traction control of space tubular shaped mandrel and detection of preform braiding angle
Authors: Jiyong Fan , Yujing Zhang , Zhongwei Wang , Zhiguo Yang
Published: August 2022

The braiding quality of composite preforms has a significant influence on their mechanical properties. To address the difficulties in the design of the processing technology and the stability of the surface quality of the fabric during the braiding process of the spatial special-shaped mandrel, a robot control method was proposed for prefabrication. Regarding branding of the formed body and inspection of the braiding angle of the fabric by machine vision for quality control, in this study the spatial special-shaped mandrel was discretized, the position and attitude of the tool center point were calculated, and the robot pulling speed was calculated. The calculation was performed to realize the automatic compensation of the braiding angle and, finally, the braiding angle of the fabric surface was detected by machine vision. The experimental results showed that the control method could effectively reduce the braiding angle error of the preform within ±2° through the detection of the visual inspection algorithm and could improve the quality of the preform and the detection speed of the braiding angle in actual production.
Case Studies Exemplifying the Transition to Animal Component-free Cell Culture
Authors: Weber Tilo , Wiest Joachim , Oredsson Stina , Bieback Karen
Published: August 2022

Cell culture techniques are strongly connected with modern scientific laboratories and production facilities. Thus, choosing the most suitable medium for the cells involved is vital, not only directly to optimise cell viability but also indirectly to maximise the reliability of the experiments performed with the cells. Fetal bovine or calf serum (FBS or FCS, respectively) is the most commonly used cell culture medium supplement, providing various nutritional factors and macromolecules essential for cell growth. Yet, the use of FBS encompasses a number of disadvantages. Scientifically, one of the most severe disadvantages is the lot-to-lot variability of animal sera that hampers reproducibility. Therefore, transitioning from the use of these ill-defined, component-variable, inconsistent, xenogenic, ethically questionable and even potentially infectious media supplements, is key to achieving better data reproducibility and thus better science. To demonstrate that the transition to animal component-free cell culture is possible and achievable, we highlight three different scenarios and provide some case studies of each, namely: i) the adaptation of single cell lines to animal component-free culture conditions by the replacement of FBS and trypsin; ii) the adaptation of multicellular models to FBS-free conditions; and (iii) the replacement of FBS with human platelet lysate (hPL) for the generation of primary stem/stromal cell cultures for clinical purposes. By highlighting these examples, we aim to foster and support the global movement towards more consistent science and provide evidence that it is indeed possible to step out of the currently smouldering scientific reproducibility crisis.
Modified π-shaped esophagojejunostomy in totally laparoscopic total gastrectomy: a report of 40 consecutive cases from a single center
Authors: Xing Jiadi , Xu Kai , Liu Maoxing , Gao Pin , Tan Fei , Yao Zhendan , Zhang Nan , Yang Hong , Zhang Chenghai , Cui Ming , Su Xiangqian
Published: August 2022

Objective

Intracorporeal esophagojejunostomy remains a challenging technique in totally laparoscopic total gastrectomy (TLTG) because of the lack of an established standard anastomosis method. However, π-shaped esophagojejunostomy in TLTG is reportedly safe and feasible. Therefore, we evaluated the short-term surgical outcomes of our modified π-shaped esophagojejunostomy in TLTG.

Methods

This study involved patients without neoadjuvant therapy diagnosed with gastric cancer who underwent TLTG by the same surgeon with modified π-shaped esophagojejunostomy from April 2018 to October 2019. Clinicopathologic data were collected and retrospectively analyzed.

Results

Forty patients diagnosed with gastric cancer were included. The mean operative time and estimated blood loss were 264.6 ± 56.9 minutes and 68.5 ± 53.3 mL, respectively. Postoperative flatus occurred at 4.6 ± 1.7 days. The mean time to resumption of diet was 7.4 ± 1.7 days postoperatively. One patient was diagnosed with anastomotic leakage and managed with conservative therapy. Pleural effusion was the most common complication, occurring in four (10%) patients. One patient developed intra-abdominal bleeding that required reoperation. Other complications were atrial fibrillation and wound infection. No mortality occurred during the 6-month follow-up.

Conclusions

Modified π-shaped esophagojejunostomy is safe and feasible for intracorporeal anastomosis in TLTG and showed favorable surgical outcomes in this study.
New frontiers of tendon augmentation technology in tissue engineering and regenerative medicine: a concise literature review
Authors: Makuku Rangarirai , Werthel Jean-David , Zanjani Leila Oryadi , Nabian Mohammad Hossein , Tantuoyir Marcarious M.
Published: August 2022

Tissue banking programs fail to meet the demand for human organs and tissues for transplantation into patients with congenital defects, injuries, chronic diseases, and end-stage organ failure. Tendons and ligaments are among the most frequently ruptured and/or worn-out body tissues owing to their frequent use, especially in athletes and the elderly population. Surgical repair has remained the mainstay management approach, regardless of scarring and adhesion formation during healing, which then compromises the gliding motion of the joint and reduces the quality of life for patients. Tissue engineering and regenerative medicine approaches, such as tendon augmentation, are promising as they may provide superior outcomes by inducing host-tissue ingrowth and tendon regeneration during degradation, thereby decreasing failure rates and morbidity. However, to date, tendon tissue engineering and regeneration research has been limited and lacks the much-needed human clinical evidence to translate most laboratory augmentation approaches to therapeutics. This narrative review summarizes the current treatment options for various tendon pathologies, future of tendon augmentation, cell therapy, gene therapy, 3D/4D bioprinting, scaffolding, and cell signals.
Effect of Connected and Autonomous Vehicles on Supply Chain Performance
Authors: Zhao Jie , Lee Ji Yun
Published: August 2022

This paper proposes a simulation framework that quantitatively assesses the direct and indirect effects of connected and autonomous vehicles (CAVs) on a supply chain system by varying the levels of CAV market penetration and driverless truck adoption. To quantify CAV effects on transportation network, this paper first collects secondary data and adopts simulation parameters and equations from existing literature. The results from transportation analysis are then incorporated into supply chain analysis to evaluate how CAVs would change supply chain performance measured by total travel time, greenhouse gas emissions, and supply chain cost. As the performance of supply chain systems involving perishable or semi-perishable products is highly sensitive to CAV market penetration rate and driverless truck adoption rate mainly because of reduced travel time, this paper uses fresh potato supply chain systems as an illustrative example. The case study results indicate that CAVs can greatly improve supply chain performance directly and indirectly by decreasing total travel time and supply chain costs, whereas emissions are reduced primarily through the adoption of driverless trucks in the supply chain system. The effect of CAVs on supply chain performance becomes even greater when commodities travel longer distances. This study will allow supply chain managers (and grocery delivery companies) to better understand how supply chain design and operation could be transformed and reoptimized in response to the introduction of CAV technologies. The research outcomes would help them better utilize the opportunities and address possible challenges that may arise as a result of CAVs.
Changes in body weight and serum cholesterol after heart transplant in relation to ventricular assist device implantation
Authors: Miura Kyoko , Yu Regina , Entwistle Timothy R , McKenzie Scott C , Green Adèle C
Published: August 2022

Weight gain is common after implantation of a ventricular assist device (VAD) prior to heart transplantation, but post-transplant changes in weight and also in blood lipids in those with VAD is virtually unknown. This study aimed to determine the influence of pre-transplant VAD implantation on body weight, blood cholesterol and triglyceride levels in Australian adult heart transplant recipients (HTRs), 1990–2017, from time of transplantation to 36 months post-transplantation. Information on VAD implantation, weight and blood lipids was collected for HTRs from medical records. Changes in weight and blood lipids from post-transplant to 12-, 24 and 36 months later, were assessed by VAD status using linear mixed-effects models. Of 236 heart transplant recipients, 48 (20%) had VAD implants. HTRs irrespective of VAD status, tended to increase their mean weight ( p < 0.001) over 36 months (VAD implant: 76.9–84.4 kg; no VAD: 81.3–88.2 kg). Patients with VAD tended to have lower mean blood lipids but experienced increases similar to those with no VAD, from baseline to 36 months (cholesterol: VAD: 4.24–4.66 mmol/l; no VAD: 4.73–4.88 mmol/l; p = 0.05; triglycerides: VAD 1.59–1.63 mmol/l; no VAD 1.85–2.22 mmol/l; p = 0.09). We conclude that HTRs in general experience weight gain and lipid increases in the first 36 months after transplantation, regardless of prior VAD implantation.
The Twenty Five Most Important Studies in Health Promotion
Authors: Terry Paul E
Published: August 2022

Which are the studies, special reports and commentaries that have been most influential in shaping the health promotion profession? This editorial poses that question to many of America’s most accomplished researchers. Each was asked to name one or two ‘must read’ studies from other scholars as well as to feature one of their own research projects that has had the greatest reach. This review of seminal studies focuses on community health, patient education and behavior change research and a future editorial will focus on workplace based health promotion research. Readers are challenged to review the four decades of research represented by this list and consider whether trends can be identified with respect to the relative attention researchers are giving to individual, interpersonal, community and societal factors influencing health behavior. How clear is the evidence that the choices we make are determined by the choices we have?
Research on prediction model of forming mechanical behavior of the dimpled tube based on the response surface methodology
Authors: Xie Shuai , Guo Zhengwei , Gong Yinchun , Ren Liancheng , Dong Chaoqun , Yang Yong
Published: August 2022

A new multi-pitch extrusion machine for producing the enhanced heat transfer tube with dimples is proposed for the first time. The goal of the present study is to investigate the forming mechanism and establish a mechanical behavior prediction model for dimpled tubes. The response surface methodology with central composite design was adopted to identify the relationships between independent variables (extrusion depth, pitch, and teeth radius) and responses (stress, plastic strain, and excursion force). The validity of the finite element model and prediction model was verified experimentally and by the analysis of variance technique. The results show that dimples and protrusions are caused by the tube wall bending inward and outward, respectively. The stress, plastic strain, and excursion force increased with increasing extrusion depth, and decreased with increasing extrusion pitch. The changes in teeth radius had no influence on the excursion force.
Following Other People’s Footsteps: A Contextual-Attraction Effect Induced by Biological Motion
Authors: Cheng Yuhui , Liu Wenjie , Yuan Xiangyong , Jiang Yi
Published: August 2022

Our visual system is bombarded with numerous social interactions that form intangible social bonds among people, as exemplified by synchronized walking in crowds. Here, we investigated whether these perceived social bonds implicitly intrude on visual perception and induce a contextual effect. Using multiple point-light walkers and a classical contextual paradigm, we tested 72 college-age adults across six experiments and found that the perceived direction of the central walker was attracted toward the direction of the surrounding walkers. The observed contextual-attraction effect occurred even when the surrounding walkers differed from the central walker in gender and walking speed but disappeared when they were asynchronously presented or replaced by inanimate motion. Strikingly, this contextual-attraction effect partially persisted in the context of local motion rather than static figures. These findings, in contrast to the typical contextual-repulsion effect, lend support for the distinctiveness of perceived social bonds on contextual modulation and suggest a specialized contextual mechanism tuned to social factors.
Urinary metabolomics study of vancomycin-associated nephrotoxicity based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry
Authors: Cao Pei , Kang Yu , Liu Jian , Liu Xiuju , Jin Yiran , Zhang Zhiqing
Published: August 2022

Drug-induced nephrotoxicity is widespread and seriously affects human health. Vancomycin is a classical glycopeptide antibiotic. Vancomycin is widely used for severe infections caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus but its obvious nephrotoxicity affects the safety of its clinical application. However, the etiology of vancomycin induced kidney injury is not well understood. This study aimed to explore the potential mechanism of vancomycin-induced nephrotoxicity in rats. Vancomycin (400 mgkg−1) was used to establish kidney injury models in rats. A metabonomic approach was employed using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to delineate metabolic alterations. As a result, 15, 22, and 37 biomarkers were identified in urine samples from the treatment group compared to the control model on D2, D4, and D7, respectively. Changes in the levels of these metabolites indicated that amino acid metabolism and energy metabolism were disturbed in rats with vancomycin-associated nephrotoxicity. This study revealed the kidney effect of vancomycin, which may provide novel and promising research approaches to vancomycin-induced renal toxicity.
E-waste Awareness and Management Among People Engaged in E-waste Selling, Collecting, Dismantling, Repairing, and Storing Activities in Addis Ababa, Ethiopia
Authors: Ali Adane Sirage , Akalu Zelalem Kibert
Published: August 2022

Associated with the increasing demand and supply of short life-span electrical devices, e-waste generation is rapidly increasing. This created a special business for some informal groups: dismantlers, e-waste sellers, repairers, and storekeepers. The objective of this study was to assess the awareness, management strategies, and associated influencing factors among the central role players of the e-waste-related business. A cross-sectional study was used to assess the awareness and management of 345 purposely selected e-waste workers including all those who are actively engaged in e-waste buying, selling, dismantling, storing, and transferring. A questionnaire was used to obtain the required information. The findings show that about 92% of the dismantlers, 70% of the sellers, and 55% of the repair and maintenance workers have poor awareness. The awareness level of the respondents is strongly associated with the newness of the issue ( V = 0.64) and lack of concern ( V = 0.44), and moderately associated with educational status ( V = 0.31), their lack of access to information (0.31), job type (0.28) and income level (0.26). The e-waste management among the study groups was limited to unsafe disposal (50%), unsafe storage (36%), and transfer (14%) to other users. The analysis showed that there is a statistically significant association between their job type and management systems (chi2 (6) = 139, P < .005, V = 0.45). Cramer’s V ( V = 0.45) shows a strong association between their job type and the e-waste management strategies. The awareness level of the respondents is very poor and influenced by several complex factors. During the study period, no study groups were practicing any of the proper e-waste management at all.
Early Outcomes of Endoscopic Papillary Muscle Relocation for Secondary Mitral Regurgitation Type IIIb in Patients With Severe Left Ventricular Dysfunction
Authors: Pausch Jonas , Bhadra Oliver D. , Sequeira Gross Tatiana M. , Hua Xiaoqin , Conradi Lenard , Reichenspurner Hermann , Girdauskas Evaldas
Published: August 2022

Objective: Subannular mitral valve (MV) repair techniques have been developed to address increased rates of recurrent mitral regurgitation (MR) in patients with secondary MR (SMR) type IIIb. Endoscopic papillary muscle relocation (PMR) is feasible via minithoracotomy. Nevertheless, the periprocedural outcome of patients with severe left ventricular (LV) dysfunction remains unknown. Methods: A total of 98 consecutive patients with SMR type IIIb underwent PMR at our institution. Due to concomitant coronary artery bypass grafting, 62 patients underwent sternotomy and were excluded from the current analysis, whereas 36 patients were treated by a minimally invasive technique using 3-dimensional endoscopy. Of these, 18 patients had severely depressed LV ejection fraction (LVEF) ≤35% (study group) and were compared to the remaining 18 patients with LVEF >35% (control group). Periprocedural outcome was retrospectively analyzed. Results: Although LVEF was significantly worse in the study group (30% ± 4% vs 43% ± 6%, P < 0.001), the severity of SMR and the degree of MV leaflet tethering were similar. The prevalence of concomitant procedures and the duration of surgery, cardiopulmonary bypass, and aortic cross-clamp were comparable. Periprocedural low cardiac output syndrome was favorably low in both groups (16.7% vs 5.6%, P = 0.29). Postoperative ventilation time (5.7 h [4.2 to 8.7 h] vs 6.0 h [4.6 to 9.8 h], P = 0.43) and duration of intensive care unit stay (2 days [1 to 3 days] vs 2 days [1 to 3 days], P = 0.22) were similar. There was no 30-day mortality in either group. Conclusions: Standardized endoscopic PMR resulted in favorable periprocedural outcomes in patients with severe LV dysfunction, suggesting that minimally invasive surgery can safely be extended to this patient population.
Twenty-first century oocyte cryopreservation—in vitro maturation of immature oocytes from ovarian tissue cryopreservation in cancer patients: A systematic review
Authors: Mohd Faizal Ahmad , Sugishita Yodo , Suzuki-Takahashi Yuki , Iwahata Hideyuki , Takae Seido , Horage-Okutsu Yuki , Suzuki Nao
Published: August 2022

Objectives:

Our review aimed to consolidate the latest update on the application of in vitro maturation among immature oocyte harvest in combination with ovarian tissue cryopreservation known as ovarian tissue oocyte–in vitro maturation.

Methods:

A thorough search for relevant studies was conducted via PubMed, Google Scholar, EMBASE, and clinical.gov databases up to December 2020. The primary outcome was the oocyte maturation rate, which measured the number of immature oocytes (geminal vesicle stage) that progressed to mature oocytes (meiosis II stage) following in vitro maturation. The secondary outcomes were the fertilization rate following intracytoplasmic sperm injection/in vitro fertilization of these oocytes for the embryo cryopreservation cohort. Our review included pre-pubertal girls and women with cancer who underwent ovarian tissue oocyte–in vitro maturation as fertility preservation.

Results:

The primary search identified 207 studies. Twelve manuscripts were selected for inclusion in our review following duplication assessment, title and abstract screening, and full-text evaluation tailored to our inclusion criteria. All the population belonged to a cancer group and underwent concurrent ovarian tissue oocyte–in vitro maturation. A total of 5724 immature oocytes were obtained following ovarian tissue cryopreservation. Approximately 33.84% of the immature oocytes successfully matured via in vitro maturation, which were cryopreserved as oocytes or fertilized as embryos and subsequently stored for future use.

Conclusion:

Our review proposed the potential application of ovarian tissue oocyte–in vitro maturation in increasing the number of mature oocytes. The acceptable improvement in oocyte maturation rate following in vitro maturation indicates that improving oocyte outcomes is an excellent cost-effective strategy for fertility preservation among women with cancer.
Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis
Authors: Choudhury Arup , Tariq Raseen , Jena Anuraag , Vesely Elissa Kinzelman , Singh Siddharth , Khanna Sahil , Sharma Vishal
Published: August 2022

Background:

Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.

Objectives:

To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID.

Design:

A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed.

Data Sources and Methods:

Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages ‘meta’ and ‘metafor’.

Results:

A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06–0.22, I2 = 99%] and 0.22 (95% CI, 0.10–0.41, I2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04–0.38, I2 = 96%), 0.06 (95% CI, 0.03–0.11, I2 = 98%), 0.20 (95% CI, 0.08–0.43, I2 = 98%), and 0.17 (95% CI, 0.10–0.27, I2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04–0.23, I2 = 98%), 0.20 (95% CI, 0.06–0.50, I2 = 97%), and 0.17 (95% CI, 0.06–0.37, I2 = 96%), respectively.

Conclusion:

GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.
Norm Values of Muscular Strength Across the Life Span in a Healthy Swiss Population: The COmPLETE Study
Authors: Lichtenstein Eric , Wagner Jonathan , Knaier Raphael , Infanger Denis , Roth Ralf , Hinrichs Timo , Schmidt-Trucksaess Arno , Faude Oliver
Published: August 2022

Background:

Grip strength is used to estimate whole-body strength for health surveillance purposes. Explosive strength is considered important, yet economic measures able to detect early deterioration of neuromuscular capabilities are lacking. Whether handgrip maximum rate of force development (GRFD) or whole-body strength tests are better predictors of lower body power than handgrip maximum strength (GFmax) and their trajectories throughout the life span are unknown.

Hypothesis:

GRFD should be more closely related to lower body power than GFmax, and its trajectories over the life span should more closely follow that of lower body power.

Study Design:

Cross-sectional.

Level of Evidence:

Level 2b.

Methods:

A total of 613 healthy participants aged 20 to 91 years were tested for countermovement jump peak power, GFmax, handgrip rate of force development, and midthigh pull peak force (MTP). Cubic splines and linear models were built for age trajectories, generalized additive models for quintile curves, and linear regression was used to assess predictive quality.

Results:

Peak power (Pmax) declined linearly to 60% of young adult level, with GRFD, GFmax, and MTP remaining stable up to age 50 years and then declining more sharply to 52% to 71% of young adult levels. Trajectories were similar for male and female participants. GRFD (β = 0.17) and MTP (β = 0.08) were worse predictors of Pmax than GFmax (β = 0.24) in models adjusted for age, sex, lean body mass, and vigorous physical activity levels.

Conclusion:

GRFD was not superior to maximum strength in predicting lower body power. For health surveillance purposes, it therefore appears that GFmax tests are more economical and equally good predictors of lower body explosive strength at older age. The data provided can be used as norm values for healthy subjects.

Clinical Relevance:

Incorporating countermovement jump testing for early detection of declines in explosive capabilities might be advised.
Vicarious Experiences of Major Discrimination and Psychological Distress among Black Men and Women
Authors: Moody Myles D. , Thomas Tobin Courtney S. , Erving Christy L.
Published: August 2022

Racism-related stress frameworks posit that the discriminatory experiences of one’s loved ones may threaten one’s well-being, but relatively few studies have examined how they may impact mental health beyond childhood and adolescence. Using data from the Nashville Stress and Health Study ( N = 1,252), the present study assessed the prevalence of vicarious experiences of discrimination among subsamples of Black men ( n = 297) and women ( n = 330), examined the association between vicarious experiences of discrimination and psychological distress among Black men and women, and evaluated the impact of vicarious discrimination on psychological distress in the context of other stressors. Results suggest that Black women report more vicarious exposure to specific types of discrimination. Furthermore, vicariously experienced discrimination was associated with higher levels of psychological distress among Black women, but not among Black men. Our findings extend the literature on racism-related stress and offer new insights for interventions aimed at reducing racial disparities in mental health.
Effect of Frequency Response Manipulations on Musical Sound Quality for Cochlear Implant Users
Authors: Mo Jonathan , Jiam Nicole T. , Deroche Mickael L.D. , Jiradejvong Patpong , Limb Charles J.
Published: August 2022

Cochlear implant (CI) users commonly report degraded musical sound quality. To improve CI-mediated music perception and enjoyment, we must understand factors that affect sound quality. In the present study, we utilize frequency response manipulation (FRM), a process that adjusts the energies of frequency bands within an audio signal, to determine its impact on CI-user sound quality assessments of musical stimuli. Thirty-three adult CI users completed an online study and listened to FRM-altered clips derived from the top songs in Billboard magazine. Participants assessed sound quality using the MUltiple Stimulus with Hidden Reference and Anchor for CI users (CI-MUSHRA) rating scale. FRM affected sound quality ratings (SQR). Specifically, increasing the gain for low and mid-range frequencies led to higher quality ratings than reducing them. In contrast, manipulating the gain for high frequencies (those above 2 kHz) had no impact. Participants with musical training were more sensitive to FRM than non-musically trained participants and demonstrated preference for gain increases over reductions. These findings suggest that, even among CI users, past musical training provides listeners with subtleties in musical appraisal, even though their hearing is now mediated electrically and bears little resemblance to their musical experience prior to implantation. Increased gain below 2 kHz may lead to higher sound quality than for equivalent reductions, perhaps because it offers greater access to lyrics in songs or because it provides more salient beat sensations.
Filling the Gaps in an Inadequate Housing Safety Net: The Experiences of Informal Housing Providers and Implications for Their Housing Security, Health, and Well-Being
Authors: Keene Danya E. , Schlesinger Penelope , Carter Shannon , Kapetanovic Amila , Rosenberg Alana , Blankenship Kim M.
Published: August 2022

The authors examine the experiences of informal housing providers, defined as those who provide housing and shelter to family, friends, and acquaintances in the context of a severe affordable rental housing crisis. Forty-five semistructured interviews were conducted with informal housing providers in and around New Haven, Connecticut, in 2021. The data describe the critical role informal housing providers play in addressing gaps in the housing safety net. Interviews also show the ways informal housing provision can strain already vulnerable households and threaten providers’ own housing security, with implications for their health and well-being. As such, the data illustrate how widespread unmet housing needs can reverberate across networks and communities. Given the multiple ways structural racism has constrained housing access for nonwhite Americans, this burden of housing provision is also likely to be unequal, with implications for population health equity.
Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias
Authors: Poplineau Mathilde , Platet Nadine , Mazuel Adrien , Hérault Léonard , N’Guyen Lia , Koide Shuhei , Nakajima-Takagi Yaeko , Kuribayashi Wakako , Carbuccia Nadine , Haboub Loreen , Vernerey Julien , Oshima Motohiko , Birnbaum Daniel , Iwama Atsushi , Duprez Estelle
Published: August 2022

Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant of acute promyelocytic leukemia, resistant to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells. We identified a subset of cells resistant to RA with proliferation, DNA replication, and repair signatures that depend on a fine-tuned E2F transcriptional network targeting the epigenetic regulator enhancer of zeste homolog 2 (EZH2). Epigenomic and functional analyses validated the driver role of EZH2 in RA resistance. Targeting pan-EZH2 activities (canonical/noncanonical) was necessary to eliminate leukemia relapse-initiating cells, which underlies a dependency of resistant cells on an EZH2 noncanonical activity and the necessity to degrade EZH2 to overcome resistance. Our study provides critical insights into the mechanisms of RA resistance that allow us to eliminate treatment-resistant leukemia cells by targeting EZH2, thus highlighting a potential targeted therapy approach. Beyond RA resistance and acute promyelocytic leukemia context, our study also demonstrates the power of single-cell multiomics to identify, characterize, and clear therapy-resistant cells.
The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM
Authors: Stong Nicholas , Ortiz-Estévez María , Towfic Fadi , Samur Mehmet , Agarwal Amit , Corre Jill , Flynt Erin , Munshi Nikhil , Avet-Loiseau Hervé , Thakurta Anjan
Published: August 2022

Although translocation events between chromosome 4 (NSD2 gene) and chromosome 14 (immunoglobulin heavy chain [IgH] locus) (t(4;14)) is considered high risk in newly diagnosed multiple myeloma (NDMM), only ∼30% to 40% of t(4;14) patients are clinically high risk. We generated and compared a large whole genome sequencing (WGS) and transcriptome (RNA sequencing) from 258 t(4;14) (n = 153 discovery, n = 105 replication) and 183 non-t(4;14) NDMM patients with associated clinical data. A landmark survival analysis indicated only ∼25% of t(4;14) patients had an overall survival (OS) <24 months, and a comparative analysis of the patient subgroups identified biomarkers associated with this poor outcome, including translocation breakpoints located in the NSD2 gene and expression of IgH-NSD2 fusion transcripts. Three breakpoints were identified and are designated as: “no-disruption” (upstream of NSD2), “early-disruption” (in the 5' UTR), and “late-disruption” (within the NSD2 gene). Our results show a significant difference in OS based on the location of DNA breakpoints (median OS 28.6 “late-disruption” vs 59.2 “early disruption” vs 75.1 months “no disruption”). These findings have been replicated in an independent replication dataset. Also, univariate and multivariate analysis suggest high-risk markers such as del17p, 1p independently contribute to poor outcome in t(4;14) MM patients.
Therapeutic targeting of PRAME with mTCRCAR T cells in acute myeloid leukemia
Authors: Kirkey Danielle C. , Loeb Anisha M. , Castro Sommer , McKay Cyd Nourigat , Perkins LaKeisha , Pardo Laura , Leonti Amanda R. , Tang Thao T. , Loken Michael R. , Brodersen Lisa Eidenschink , Loeb Keith R. , Scheinberg David A. , Le Quy , Meshinchi Soheil
Published: August 2022

Preferentially Expressed Antigen in Melanoma (PRAME), a cancer-testis antigen, provides an ideal target for immunotherapy in acute myeloid leukemia (AML). We have shown expression of PRAME in a significant subset of childhood and adult AML and lack of expression in normal hematopoiesis. Although an intracellular antigen, we developed a novel approach to target PRAME using a chimeric antigen receptor (CAR) construct encoding a targeting domain based on T-cell receptor (TCR) mimic antibodies that target the peptide-HLA complex. We used the antibody sequence from a previously designed TCR mimic (mTCR) antibody, Pr20, that recognizes the PRAME ALY peptide in complex with HLA-A∗02 and verified expression of PRAME in AML cell lines and primary AML blasts. Using the Pr20 antibody sequence, we developed CAR T cells (PRAME mTCRCAR T) to be tested against primary samples from patients with AML and AML cell lines that express the PRAME antigen in the context of HLA-A2 expression. In contrast to appropriate controls, PRAME mTCRCAR T cells demonstrate target-specific and HLA-mediated in vitro activity in OCI-AML2 and THP-1 cell lines, HLA-A2 cell lines expressing the PRAME antigen, and against primary AML patient samples. In vivo cell-derived xenograft models treated with PRAME mTCRCAR T cells demonstrated potent leukemia clearance and improved survival compared with unmodified T-cell controls. Furthermore, the cytolytic activity of PRAME mTCRCAR T cells was enhanced by treating the target cells with interferon gamma, which increases PRAME antigen expression. These results demonstrate the feasibility and efficacy of targeting PRAME with novel PRAME mTCRCAR T cells.
Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients
Authors: Sasso Etianne Martini , Muraki Katsuhiko , Eaton-Fitch Natalie , Smith Peter , Lesslar Olivia Ly , Deed Gary , Marshall-Gradisnik Sonya
Published: August 2022

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystemic condition associated with post-infectious onset, impaired natural killer (NK) cell cytotoxicity and impaired ion channel function, namely Transient Receptor Potential Melastatin 3 (TRPM3). Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has resulted in neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations recently recognised as post coronavirus disease 2019 (COVID-19) condition. The symptomatology of ME/CFS overlaps significantly with post COVID-19; therefore, this research aimed to investigate TRPM3 ion channel function in post COVID-19 condition patients.

Methods

Whole-cell patch-clamp technique was used to measure TRPM3 ion channel activity in isolated NK cells of N = 5 ME/CFS patients, N = 5 post COVID-19 patients, and N = 5 healthy controls (HC). The TRPM3 agonist, pregnenolone sulfate (PregS) was used to activate TRPM3 function, while ononetin was used as a TRPM3 antagonist.

Results

As reported in previous research, PregS-induced TRPM3 currents were significantly reduced in ME/CFS patients compared with HC (p = 0.0048). PregS-induced TRPM3 amplitude was significantly reduced in post COVID-19 condition compared with HC (p = 0.0039). Importantly, no significant difference was reported in ME/CFS patients compared with post COVID-19 condition as PregS-induced TRPM3 currents of post COVID-19 condition patients were similar of ME/CFS patients currents (p > 0.9999). Isolated NK cells from post COVID-19 condition and ME/CFS patients were resistant to ononetin and differed significantly with HC (p < 0.0001).

Conclusion

The results of this investigation suggest that post COVID-19 condition patients may have impaired TRPM3 ion channel function and provide further evidence regarding the similarities between post COVID-19 condition and ME/CFS. Impaired TRPM3 channel activity in post COVID-19 condition patients suggest impaired ion mobilisation which may consequently impede cell function resulting in chronic post-infectious symptoms. Further investigation into TRPM3 function may elucidate the pathomechanism, provide a diagnostic and therapeutic target for post COVID-19 condition patients and commonalities with ME/CFS patients.
Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting
Authors: Al-Azab Mahmoud , Safi Mohammed , Idiiatullina Elina , Al-Shaebi Fadhl , Zaky Mohamed Y.
Published: August 2022

Human mesenchymal stem cells (MSCs) are primary multipotent cells capable of differentiating into osteocytes, chondrocytes, and adipocytes when stimulated under appropriate conditions. The role of MSCs in tissue homeostasis, aging-related diseases, and cellular therapy is clinically suggested. As aging is a universal problem that has large socioeconomic effects, an improved understanding of the concepts of aging can direct public policies that reduce its adverse impacts on the healthcare system and humanity. Several studies of aging have been carried out over several years to understand the phenomenon and different factors affecting human aging. A reduced ability of adult stem cell populations to reproduce and regenerate is one of the main  contributors to the human aging process. In this context, MSCs senescence is a major challenge in front of cellular therapy advancement. Many factors, ranging from genetic and metabolic pathways to extrinsic factors through various cellular signaling pathways, are involved in regulating the mechanism of MSC senescence. To better understand and reverse cellular senescence, this review highlights the underlying mechanisms and signs of MSC cellular senescence, and discusses the strategies to combat aging and cellular senescence.

Graphical Abstract
Activated TRPA1 plays a therapeutic role in TMZ resistance in glioblastoma by altering mitochondrial dynamics
Authors: Chen Hao , Li Chunlin , Hu Haiyang , Zhang Bin
Published: August 2022

Background

Glioblastoma (GBM) represents nearly one-half of primary brain tumors, and the median survival of patients with GBM is only 14.6 months. Surgery followed by radiation with concomitant temozolomide (TMZ) therapy is currently the standard of care. However, an increasing body of evidence suggests that GBM acquires resistance to TMZ, compromising the effect of the drug. Thus, further exploration into the mechanism underlying this resistance is urgently needed. Studies have demonstrated that TMZ resistance is associated with DNA damage, followed by altered reactive oxygen species (ROS) production in mitochondria. Studies have also showed that Ca2+-related transient receptor potential (TRP) channels participate in GBM cell proliferation and metastasis, but the detailed mechanism of their involvement remain to be studied. The present study demonstrates the role played by TRPA1 in TMZ resistance in GBM and elucidates the mechanism of resistance.

Methods

U251 and SHG-44 cells were analyzed in vitro. A CCK-8 assay was performed to verify the effect of TMZ toxicity on GBM cells. Intracellular ROS levels were detected by DCFH-DA assay. A MitoSOX Red assay was performed to determine the mitochondrial ROS levels. Intracellular Ca2+ levels in the cells were determined with a Fluo-4 AM calcium assay kit. Intracellular GSH levels were determined with GSH and GSSG Assay Kit. MGMT protein, Mitochondrial fission- and fusion-, apoptosis- and motility-related protein expression was detected by western blot assay. A recombinant lentiviral vector was used to infect human U251 cells to overexpress shRNA and generate TRPA1+/+ and negative control cells. All experiments were repeated.

Results

In the U251 and SHG-44 cells, TMZ induced a small increase in the apoptosis rate and intracellular and mitochondrial ROS levels. The expression of antioxidant genes and antioxidants in these cells was also increased by TMZ. However, pretreatment with a TRPA1 agonist significantly decreased the level of antioxidant gene and antioxidants expression and enhanced intracellular and mitochondrial ROS levels. Also TMZ induced the level of MGMT protein increased, and pretreatment with a TRPA1 agonist decreased the MGMT expression. Moreover, Ca2+ influx, mitochondrial damage and cell apoptosis were promoted, and the balance between mitochondrial fission and fusion protein expression was disrupted in these GBM cells. Pretreatment with a TRPA1 inhibitor slightly enhanced the level of antioxidant gene expression and reduced the apoptosis rate. TRPA1 gene overexpression in the U251 cells was similar to that after inhibitor intervention, confirming the aforementioned experimental results.

Conclusion

The present study proved that activating TRPA1 in glioma cells, which leads to mitochondrial damage and dysfunction and ultimately to apoptosis, may decrease the TMZ resistance of GBM cells.
Comment on: “Pecto-intercostal Fascial Block for perioperative pain management in patients undergoing open cardiac surgery”
Authors: Sethuraman Raghuraman M.
Published: August 2022

This article (Correspondence) is in response to the recently published article on the role of Pecto-intercostal Fascial Block for cardiac procedures by Zhang et al. in “BMC Anesthesiology”. I greatly appreciate the authors for publishing this study in which Pecto-intercostal Fascial Block, a novel technique for providing pain relief in open cardiac surgical procedures was evaluated. I wish to present my reflections on this article as well as to add a few more points on this topic.
Association of visceral fat area with pre-frailty in Japanese community-dwelling older adults: a cross-sectional study
Authors: Su Ya , Yuki Michiko , Ogawa Natsuka
Published: August 2022

Background

Screening and intervention in pre-frailty can help prevent or delay frailty among older adults. Being overweight has shown associated with pre-frailty, and overweight is highly prevalent among community-dwelling older adults during COVID-19. However, the impact of visceral fat accumulation remains unclear. This study aimed to explore the association between visceral fat area and pre-frailty in community-dwelling older adults.

Methods

The participants of this study included community-dwelling older adults from three elderly welfare centers. The frailty phenotype was assessed using the frailty screening index. The body composition was measured using bioelectrical impedance analysis.

Results

A total of 214 community-dwelling older adults completed the questionnaire and measurements. After excluding 16 frail participants, 149 (75.3%) were pre-frailty. The mean age of participants was 75.4 ± 5.4 years, and 69.7% (138) of participants were women. There were 54 (27.3%) participants with high visceral fat area. The multivariable model showed that participants with high visceral fat area were at increased risk for pre-frailty (adjusted OR, 3.15; 95% CI, 1.26 − 7.87; P = 0.014), even after adjusted for age, sex, health status, and impact of COVID-19 pandemic.

Conclusions

This study suggests that the association between visceral fat accumulation and pre-frailty may help to identify a new target for prevention. Further longitudinal studies are needed to determine their mechanisms in older adults.
Tuberculosis dissemination in kidney transplant recipient treated with anti-CD40 monoclonal antibody: a case report
Authors: Bednarova Kamila , Slatinska Janka , Fabian Ondrej , Wohl Pavel , Kopecka Emilia , Viklicky Ondrej
Published: August 2022

Background

Tuberculosis (TBC) in solid organ transplant recipients represents a severe complication. The incidence among transplant recipients is higher than in the general population, and the diagnosis and treatment remain challenging. We present a case of active disseminated tuberculosis in a kidney transplant recipient treated with an anti-CD40 monoclonal antibody, who had been previously exposed to an active form of the disease, but latent tuberculosis (LTBI) was repeatedly ruled out prior to transplantation. To the best of our knowledge, no other case has been reported in a patient treated with the anti-CD40 monoclonal antibody.

Case presentation

A 49-year-old patient, 1.5 years after primary kidney transplantation, presented with vocal cord problems, a dry irritating cough, and a sore throat. A detailed investigation, including a high-resolution chest CT scan, revealed the diagnosis of disseminated tuberculosis. The antituberculosis treatment consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol was started immediately. The patient's condition became complicated by relapsing diarrhoea. The colonoscopy revealed a circular stenosis above Bauhin’s valve. Microscopical findings showed active colitis and vaguely formed collections of epithelioid macrophages without fully developed caseous granulomas and were consistent with the clinical diagnosis of tuberculosis. The antituberculosis treatment was subsequently enhanced by moxifloxacin and led to a great improvement in the patient’s condition.

Conclusion

In this case, false negativity of interferon-γ release assays and possibly higher risk for intracellular infections in patients on costimulatory signal blockers are discussed.