bluuebunny/crossref_metadata_2025 huggingface dataset:
Tbx18 promoted the conversion of human‐induced pluripotent stem cell‐derived cardiomyocytes into sinoatrial node‐like pacemaker cells
Authors: Zhang Wei , Zhao Hongyi , Quan Dajun , Tang Yanhong , Wang Xi , Huang Congxin
Published: December 2021

Sinoatrial node (SAN) pacemaker cells originate from T‐box transcription factor 18 (Tbx18)‐expressing progenitor cells. The present study aimed to investigate whether overexpression of human transcription factor Tbx18 could reprogram human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) into SAN‐like pacemaker cells (SANLPCs) in vitro. In the study, hiPSCs were first differentiated into hiPSC‐CMs through regulating the Wnt/β‐catenin pathway, then purified hiPSC‐CMs were transfected by Tbx18 adenovirus (Tbx18‐CMs group) or green fluorescent protein (GFP) adenovirus (GFP‐CMs group). The beating frequency of the Tbx18‐CMs group was significantly higher than that of the hiPSC‐CMs group and GFP‐CMs group. Compared with the other two groups, the expression levels of hyperpolarization‐activated cyclic nucleotide‐gated potassium channel isoform 4, connexin‐45 in the Tbx18‐CMs group were markedly upregulated, while the expressions of transcription factor NKX2.5, CX43 were significantly downregulated. Whole‐cell patch‐clamp results illustrated that action potential and “funny” current (If) similar to SAN pacemaker cells could be recorded in the Tbx18‐CMs group. In conclusion, this present study demonstrated that overexpression of Tbx18 promoted the conversion of hiPSC‐CMs into SANLPCs.
Research progress of Bub3 gene in malignant tumors
Authors: Wang Chenyang , Cheng Dating , Pan Chenglong , Wang Chunyan , Nie Zhi
Published: December 2021

The spindle assembly checkpoint (SAC) is a highly conserved monitoring system that ensures a fidelity of chromosome segregation during mitosis. Bub3, a mitotic Checkpoint Protein, is a member of the Bub protein family, and an important factor in the SAC. Abnormal expression of Bub3 results in mitotic defects, defective spindle gate function, chromosomal instability and the development of aneuploidy cells. Aneuploidy is a state of abnormal karyotype that has long been considered as a marker of tumorigenesis. Karyotypic heterogeneity in tumor cells, known as “chromosomal instability” (CIN), can be used to distinguish cancerous cells from their normal tissue counterpart. In this review, we summarize the expression and clinical significance of Bub3 in a variety of tumors and suggest that it has potential in the treatment of cancer.
HPV16 E6/E7 stabilize PGK1 protein by reducing its poly‐ubiquitination in cervical cancer
Authors: Liu Shikai , Song Lili , Yao Hairong , Zhang Liang
Published: December 2021

This study aimed to explore the expression profile, prognostic value, regulatory effect, and the underlying mechanism of dysregulation of phosphoglycerate kinase 1 (PGK1) in high‐risk human papillomavirus (HPV)‐positive cervical epithelial squamous cell carcinoma (CESC). Bioinformatic analysis was performed using the CESC subset of The Cancer Genome Atlas (TCGA)‐Cervical Cancer (CESC) and normal cervix in The Genotype‐Tissue Expression (GTEx) project. HPV‐16 positive CaSki and SiHa cells were used as in vitro cell models. Results showed that compared to the normal cervix, CESC tissues had significantly higher expression of PGK1. CESC patients with the higher 50% expression of PGK1 had substantially shorter disease‐specific survival (DSS), and progression‐free survival (PFS) compared to the cases with the lower 50% expression of PGK1. PGK1 knockdown impaired, but PGK1 overexpression enhanced the proliferation, colony formation, aerobic glycolytic activities (lactate production, intracellular ATP levels, glucose uptake, and extracellular acidification rate), migration, and invasion of CaSki and SiHa cells. HPV‐16 E6/E7 knockdown in CaSki and SiHa cells had limited influence on PGK1 transcription but significantly decreased the half‐life of PGK1 protein. E6/E7 knockdown mediated PGK1 downregulation could be blocked by adding MG‐132. PGK1 poly‐ubiquitination was significantly enhanced after E6/E7 knockdown. In conclusion, this study showed that PGK1 expression might serve as a prognostic biomarker in cervical cancer. Its upregulation contributes to enhanced aerobic glycolysis, migration, and invasion of CESC cells. HPV16 E6/E7 stabilizes PGK1 protein by reducing its poly‐ubiquitination.
The identification of a novel splicing mutation in the DMD gene of a Chinese family
Authors: Liu Wanlu , Shi Xinwei , Li Yuqi , Qiao Fuyuan , Wu Yuanyuan
Published: December 2021

The proband is a five‐year‐old boy diagnosed with Duchenne muscular dystrophy (DMD) by clinical manifestations and laboratory examination, but clinical phenotype of his parents is normal. In the study, his mother had a second pregnancy, and they went to obstetrics for genetic counseling to make informed reproductive choices.
Stimuli‐Responsive Polymers with Room‐Temperature Phosphorescence
Authors: Gu Fan , Ma Xiang
Published: December 2021

Taking advantages of the impressing behaviors of room‐temperature phosphorescence (RTP), the explorations in RTP materials are not only limited to efficient emission and ultralong lifetime of phosphorescence. The discovery and creation of stimuli‐responsive properties have become the major pursuit, which will lay a solid foundation for future applications in RTP materials. Based on this, a review centered on recent progress of stimuli‐responsive RTP materials is summarized to show frontier development in polymer systems. Different kinds of stimuli‐responsive factors including light, oxygen, temperature, mechanical force and pH regulations are investigated in this review. Many potential applications and promising strategies are deeply discussed with the hope to assist future studies in this area.
Glycoenzyme Tool Development: Principles, Screening Methods, and Recent Advances†
Authors: Cui Tongxiao , Man Yi , Wang Feifei , Bi Shuyang , Lin Liang , Xie Ran
Published: December 2021

Comprehensive Summary

To elucidate the relationship between carbohydrate structure and its biological function, glycoenzyme tools are widely applied in a variety of physiological and pathological scenarios. Intricate adjustment via glycoenzyme engineering improved the catalytic efficiency, extended the repertoire of accessible catalytic reactions, and tailored novel substrate specificities. In this review, we introduce the principles of glycoenzyme engineering and summarize the recent advances in the rational design and directed evolution of these enzymes, with an emphasis on screening methods in directed evolution. We also excerpt novel detection methods in glycobiology that can be adapted for the development of next‐generation glycoenzyme tools.
Psychosocial factors associated with genetic testing status among African American women with ovarian cancer: Results from the African American Cancer Epidemiology Study
Authors: McBride Colleen M. , Pathak Sarita , Johnson Courtney E. , Alberg Anthony J. , Bandera Elisa V. , Barnholtz‐Sloan Jill S. , Bondy Melissa L. , Cote Michele L. , Moorman Patricia G. , Peres Lauren C. , Peters Edward S. , Schwartz Ann G. , Terry Paul D. , Schildkraut Joellen M.
Published: December 2021

Background

Racial disparities in the uptake of cancer genetic services are well documented among African American (AA) women. Understanding the multiple social and psychological factors that can influence the uptake of genetic testing among AA women is needed.

Methods

Data came from 270 AA women diagnosed with ovarian cancer and participating in a population‐based, case‐control study of ovarian cancer who were asked about genetic testing. Logistic regression analyses tested the associations of predisposing, enabling, and need factors with reported genetic testing uptake.

Results

One‐third of the sample (35%) reported having had genetic testing. In the multivariable model, AA women with higher incomes had more than double the odds of being tested than those with the lowest income (odds ratio [OR] for $25,000‐$74,999, 2.04; 95% confidence interval [CI], 1.06‐3.99; OR for ≥$75,000, 2.32; 95% CI, 0.92‐5.94). AA women who reported employment discrimination were significantly less likely to report genetic testing than those who did not report job discrimination (OR, 0.39; 95% CI, 0.14‐0.95). Marital status, Medicaid versus other insurance, prayer frequency, and perceived social support were significantly associated with genetic testing uptake in bivariate analyses but were not significant contributors in multivariable analyses.

Conclusions

Consistent with other studies of AA women, a minority of African American Cancer Epidemiology Study participants had undergone genetic testing. Having a lower income and experiencing job discrimination decreased the likelihood of testing. These results provide foundational evidence supporting the need for interventions to improve the uptake of genetic testing among AA women by reducing cost barriers and providing credible assurances that genetic results will be kept private and not affect social factors such as employability.
Spatial network clustering reveals elk population structure and local variation in prevalence of chronic wasting disease
Authors: Sargeant Glen A. , Wild Margaret A. , Schroeder Gregory M. , Powers Jenny G. , Galloway Nathan L.
Published: December 2021

Spatial organization plays prominent roles in disease transmission, genetics, and demography of wildlife populations and is therefore an important consideration not only for wildlife management, but also for inference about populations and processes. We used hierarchical agglomerative clustering of a spatial graph network to partition Wind Cave National Park (WICA) into five regions used by 163 female elk (Cervus elaphus) marked with global positioning system collars during 2005–08 and 2011–13. We grouped elk based on differential use of the five regions, developed a priori models for inter‐group variation in the occurrence of chronic wasting disease (CWD), and used Akaike's information criterion to compare models and stratify regions. Previous descriptions of elk population structure, which have been based on social contact or overlap of individual ranges, have distinguished spatially disjunct population subsets. Constructing hierarchical partitions of the landscape enabled us to also discern and describe overlapping and nested subsets. During 2016–18, apparent park‐wide prevalence of CWD was 0.18 (90% CI = [0.146, 0.182]); however, prevalence within three spatial strata used primarily by different elk ranged from 0.03 ([0.008, 0.074]) to 0.29 ([0.211, 0.375]). In context with published estimates of recruitment, predation, and anthropogenic mortality, such differences in prevalence equate to increasing local abundance of elk in southwestern WICA, stable to declining abundance in the west/northwest, and rapidly declining abundance in the east. Despite the modest size of WICA (11,357 ha), park‐wide averages conflate effects of elk distribution and disease, obscuring spatial patterns with profound implications for study and management of elk and CWD. Graph networks have been used widely in ecology to describe such phenomena as social relationships, connectivity of habitat patches, animal movements, and the spread of disease. Extension to partitioning of geographic range is straightforward but entails different considerations. We discuss allocation of sampling effort, construction of an initial partition, specification of a model for graph cohesion, selection of a clustering algorithm, and identification of useful partitions.
Biocrusts do not differentially influence emergence and early establishment of native and non‐native grasses
Authors: McIntyre Cheryl , Archer Steven R. , Predick Katharine I. , Belnap Jayne
Published: December 2021

Biological soil crusts (biocrusts) cover the soil surface of global drylands and interact with vascular plants. Biocrusts may influence the availability and nature of safe sites for plant recruitment and the susceptibility of an area to invasion by non‐native species. Therefore, to investigate the potential role of biocrusts in invasive species management, we sought to determine whether native and non‐native grass recruitments in two North American deserts were differentially affected by biocrusts. We conducted a series of coordinated experiments in field, semi‐controlled, and controlled environment settings in the Colorado Plateau and Sonoran Desert using contrasting biocrust and grass functional types. Experiments in field environments focused on early establishment of grass seedlings whereas controlled environment experiments focused on seedling emergence. Within each experiment, we compared responses (frequency, magnitude, and timing of emergence/establishment) both across species (biocrust types pooled) and across species and levels of biocrust development. Native grasses varied by experiment and included Aristida purpurea, A. purpurea var. longiseta, Bouteloua gracilis, and Vulpia octoflora. Emergence of non‐native Bromus tectorum was similar to that of native grasses on the Colorado Plateau. Differences in emergence of native vs. non‐native grasses in the Sonoran Desert were species‐ and response‐specific. Emergence of the non‐native Bromus rubens was comparable to that of native grasses whereas emergence frequency and magnitude of the non‐native Pennisetum ciliare was lower compared with two of four native species. Within a grass species, emergence was higher and faster on bare soil compared with biocrusts in the Sonoran Desert semi‐controlled and greenhouse environment experiments. However, the pattern was not consistent across other experiments. When comparing across Colorado Plateau and Sonoran Desert biocrusts in greenhouse experiments, we found that emergence of native grasses was higher on Colorado Plateau biocrusts. Based on the lack of consistent results across our experiments, grass recruitment on biocrusts appears to be driven more by species‐specific traits than species provenance. Our greenhouse experiments suggest that biocrust topographic relief is an important safe site trait influencing plant recruitment.
Increased salinity stress changes plant productivity and biomass by altering the top‐down controls in eelgrass beds
Authors: Namba Mizuho , Nakaoka Masahiro
Published: December 2021

Understanding biological community responses to disturbances such as extreme rainfalls under climate change is crucial when predicting ecosystem changes and functions. However, it is still unclear how species interaction changes with increasing disturbances and how disturbance susceptibility varies among organisms from habitats with different stress levels along stress gradients such as salinity gradients. We examined whether (1) higher frequency (i.e., pulse disturbance) and longer duration (i.e., press disturbance) of salinity change affected the primary producers, animals, and their interactions, and whether (2) organisms from naturally stressful habitats with unstable salinity were more tolerant to salinity changes. We used eelgrass Zostera marina, epiphytic microalgae, and grazer gastropod Lacuna decorata from two sites in each of the two lagoons; Akkeshi with a strong salinity gradient, and Notoro with a weak gradient to do indoor mesocosm experiments for testing the effects of salinity change and grazer presence on eelgrass growth and biomass of epiphytic microalgae, as well as grazer survival, growth, and consumption rates. We established treatments with low, intermediate, and high levels of salinity stress to test the effects of press and pulse disturbances in terms of salinity changes. The findings suggest the presence of a top‐down control of epiphytic microalgae by grazers. Eelgrass growth rate was higher with the presence of grazers but declined with higher salinity stress. The biomass of epiphytic microalgae was higher with the absence of grazers and with higher salinity stress across all sites. Grazer survival varied among individuals raised in habitats with naturally stable or unstable salinity regime and decreased with more frequent and longer salinity changes. Grazer growth rates and grazing rates also decreased with higher salinity stress, but grazing on epiphytic microalgae was highest at the intermediate stress levels across all sites. This study demonstrates that salinity regime shifts that are expected to occur with extreme rainfalls due to ongoing climate change could affect coastal ecosystems such as eelgrass beds, and we call for further investigations on the different stress responses of organisms raised in habitats with stable and unstable salinity to understand the potential effects of the disturbances on ecosystem function.
Altitude and community traits explain rain forest stand dynamics over a 2370‐m altitudinal gradient in Costa Rica
Authors: Hernández Gordillo Alba Lorena , Vilchez Mendoza Sergio , Ngo Bieng Marie Ange , Delgado Diego , Finegan Bryan
Published: December 2021

Stand dynamic rates in Earth's vitally important tropical mountain rain forests are a central component of the response of these forests to global change, but their relationships to environmental gradients are poorly understood. We worked in mature forests on a 440–2810 m asl altitudinal gradient on Costa Rica's Talamanca Cordillera, making five censuses of 29 0.25‐ha permanent sample plots during 2012–2019. We determined mortality and recruitment rates, as well as basal area (G) increments, for individuals ≥10 cm diameter at breast height. Our main hypothesis was that stand dynamic rates decrease with altitude (therefore temperature); we also tested the hypotheses that rates increase with plot community‐weighted mean specific leaf area (CWM SLA) and decrease with CWM wood specific gravity (WSG). We developed regressions using generalized additive models to test our hypotheses. Mortality and recruitment rates decreased with altitude in line with our main hypothesis, though the strongly non‐linear mortality trend may be driven by extreme weather and temperature. Also, the best model for recruitment rates included plot CWM SLA with a negative relationship. Gross basal area increment ∆Ggross, the annual basal area increment of trees that survived the study period, had a hump‐shaped relationship to altitude, possibly related to the low CWM WSG of mid‐altitude forests. ∆Ggross was indeed negatively related to CWM WSG. However, net basal area growth (∆Gnet, the annualized difference between initial and final plot basal areas) was positively related to altitude due to low mortality in montane forests, in a model with CWM WSG with a negative relationship. ∆Gnet was negative in nine of the 29 plots at <1500 m asl. Patterns of rain forest stand dynamics on this long altitudinal gradient go beyond a direct response to temperature, and further work is required to improve scenarios of forest response to climate change. CWM traits should be measured to improve understanding. The effects of storms and lightning on low‐ and middle‐altitude forest and the potentially high resilience of montane Fagaceae‐dominated forests require attention. Diversity, not generality, should be expected on comparing tropical forest altitudinal transects.
A Strongly Coupled Biruthenium Complex as Catalyst for the Water Oxidation Reaction
Authors: Domínguez Sofía E. , Juarez M. Virginia , Pieslinger German E. , Baraldo Luis M.
Published: December 2021

The catalytic activity towards water oxidation of a strongly coupled bimetallic ruthenium complex, trans‐[Ru(tpy)(bpy)(μ‐CN)Ru(py)4(OH2)]3+ (RuIIRuIIOH2), where tpy=2,2′:6′,2’’‐terpyridine, bpy=2,2′‐bipyridine and py=pyridine are presented. At pH 1 the first two oxidation reactions are centred at the aquo fragment and result in the RuIIRuIIIOH2 and RuIIRuIVO redox states as confirmed by its spectroscopy and DFT calculations. Oxidation by an additional electron is followed by an irreversible step and a catalytic wave associated with the water oxidation reaction. At pH 1 the reaction with an excess of Ce(IV) results in the generation of an stoichiometric amount of oxygen based on molar amounts of the added Ce(IV). The dominant species during the catalytic cycle is the three‐electron oxidized product, RuIIIRuIVO. The reduction of the concentration of Ce(IV) monitored at 370 nm follow the rate equation, −d[Ce(IV)]/dt=kox[Ce(IV)][RuIIRuIIOH2] with a kox=82±3 M−1s−1 at T=298 K. The RuIIIRuIVO species is not stable and reacts to give RuIIRuIVO.
A Comprehensive Examination of Voltammetric Parameters in Fourier Transform Sine‐wave Voltammetry (FT‐SWV) Leading to Concentration Linearity and High Signal‐to‐background Ratio
Authors: Yang Yejin , Weber Stephen G.
Published: December 2021

There has not been a comprehensive investigation of the effect of voltammetric parameters: amplitude, dc bias potential, and excitation frequency of the sine waveform in Fourier Transform Sine‐Wave Voltammtery (FT‐SWV) on background, signal, and signal‐to‐background ratio as well as linearity with respect to the concentration of an analyte. FT‐SWV of ruthenium hexamine (III) chloride (RuHex) demonstrates that the dc bias potential can be used to adjust the phase angle difference between the signal and background to obtain out‐of‐phase background. Several conditions show a high signal‐to‐noise ratio and good concentration linearity. The lessons from RuHex guided us to conditions for good signal‐to‐background ratio and concentration linearity for dopamine (DA).
Square Wave Anodic Stripping Voltammetric Determination of Hg(II) with N1‐Hydroxy‐N1,N2‐diphenylbenzamidine Modified Carbon Paste Electrode
Authors: Tesfaye Endale , Singh Chandravanshi Bhagwan , Hailu Tesfu , Negash Negussie , Tessema Merid
Published: December 2021

Mercury is a highly toxic metal, of which even small doses (<200 ng mL−1) can cause serious problems for humans, plants, animals and microorganisms, including marine species and freshwater organisms. Hence, a simple, fast, highly selective and sensitive and accurate method for the detection of mercury in the environmental, clinical or biological samples is necessary. A new, sensitive and selective method for the determination of Hg(II) with 5 % N1‐hydroxy‐N1,N2‐diphenylbenzamidine modified carbon paste electrode has been developed. Hg(II) was accumulated for 210 s on the surface of the modified electrode using 0.1 M CH3COONa of pH 7 at −0.8 V vs Ag/AgCl, followed by electrochemical stripping with SWASV in 0.1 M NH4Cl at pH 4. The linear range is 0.02–10 μM Hg(II) with limit of detection of 1.28 nM. The method has RSDs of 3.7 %. The method was applied for the determination Hg(II) in five types of water samples. The recoveries were in the range 97.8–103 %. The proposed method was found to be highly selective and sensitive and has many attractive features compared to previous reports such as low cost, simplicity of electrode preparation, long term stability, fast response, easy renewable ability, and reasonable short accumulation time.
Attention networks and the intrinsic network structure of the human brain
Authors: Markett Sebastian , Nothdurfter David , Focsa Antonia , Reuter Martin , Jawinski Philippe
Published: December 2021

Attention network theory distinguishes three independent systems, each supported by its own distributed network: an alerting network to deploy attentional resources in anticipation, an orienting network to direct attention to a cued location, and a control network to select relevant information at the expense of concurrently available information. Ample behavioral and neuroimaging evidence supports the dissociation of the three attention domains. The strong assumption that each attentional system is realized through a separable network, however, raises the question how these networks relate to the intrinsic network structure of the brain. Our understanding of brain networks has advanced majorly in the past years due to the increasing focus on brain connectivity. The brain is intrinsically organized into several large‐scale networks whose modular structure persists across task states. Existing proposals on how the presumed attention networks relate to intrinsic networks rely mostly on anecdotal and partly contradictory arguments. We addressed this issue by mapping different attention networks at the level of cifti‐grayordinates. Resulting group maps were compared to the group‐level topology of 23 intrinsic networks, which we reconstructed from the same participants' resting state fMRI data. We found that all attention domains recruited multiple and partly overlapping intrinsic networks and converged in the dorsal fronto‐parietal and midcingulo‐insular network. While we observed a preference of each attentional domain for its own set of intrinsic networks, implicated networks did not match well to those proposed in the literature. Our results indicate a necessary refinement of the attention network theory.
Muscarinic (M1) cholinergic receptor activation within the dorsal hippocampus promotes destabilization of strongly encoded object location memories
Authors: Huff Andrew E. , McGraw Shelby D. , Winters Boyer D.
Published: December 2021

Following the initial consolidation process, memories can become reactivated by exposure to a reminder of the original learning event. This can lead to the memory becoming destabilized and vulnerable to disruption or other forms of modification. The memory must then undergo the protein‐synthesis dependent process of reconsolidation in order to be retained. However, older and/or stronger memories resist destabilization, but can become labile when reactivated in the presence of salient novelty. We have implicated the neurotransmitter acetylcholine, acting at M1 muscarinic cholinergic receptors (mAChRs) within perirhinal cortex (PRh), in novelty‐induced destabilization of remote object memories. It remains unclear, however, whether mAChRs are involved in destabilization of other forms of memory. We hypothesized that the role of M1 mAChRs previously demonstrated for PRh‐dependent object memory would extend to hippocampus‐dependent spatial memory. Using the object location (OL) task, which relies on the dorsal hippocampus (dHPC), we showed that (a) reactivation‐dependent reconsolidation of OL memories requires protein synthesis within the dHPC; (b) destabilization of relatively weak OL memories depends on M1 mAChR activation within the dHPC; (c) salient novelty during reactivation promotes destabilization of resistant strongly encoded OL memories; (d) novelty‐induced destabilization of strong OL memories requires activation of mAChRs within the dHPC; and (e) M1 mAChR activation within the dHPC in the absence of novelty during memory reactivation mimics the effect of novelty, destabilizing strongly encoded OL memories. These results implicate ACh acting at M1 mAChRs in the destabilization of dHPC‐dependent spatial memories, demonstrating generalizability of this cholinergic function beyond memory for object identity. These findings therefore enhance our understanding of the dynamics of long‐term memory storage and suggest implications for the treatment of human conditions such as Alzheimer's disease and aging, which are characterized by behavioral and mnemonic inflexibility.
Deindustrialising economies, plant closures and affected communities: Identifying potential pathways to health inequities
Authors: Browne–Yung Kathryn , Ziersch Anna , Friel Sharon , Freeman Toby , Baum Fran
Published: December 2021

Issue addressed

Deindustrialisation and transitions from traditional manufacturing to new technologies and service industries in many high‐income countries including Australia has resulted in rising employment insecurity, unemployment and increased income and health inequities. In this paper, we explore potential impacts of an automotive plant closure on health in a disadvantaged area of South Australia. Our aim was to examine how prevailing factors affecting social and health inequity might be further affected following the plant closure and to identify levers for potential policy responses.

Methods

In workshop discussions with 28 policy and 14 community stakeholders through an iterative process participants discussed how existing factors contributing to community social and health inequity might be worsened (or remediated) by the looming economic shock from the plant closure.

Results

We identified eight key themes highlighted in the workshops. In particular local economic investment, availability of job opportunities, and appropriate training were identified as key factors influencing individual financial security, which was in turn linked to social and health impacts.

Conclusions

The pathways mapped between the plant closure and social and health equity impacts highlighted differential potential impacts on individuals and the community, and identified policy levers to reduce adverse health outcomes resulting from economic shocks such as the closure of a major employer.

So what?

The study highlighted a broad range of intersecting factors affecting the health of the local community that policy responses to the plant closure needed to address to promote health and health equity. This included novel factors identified by community members, reinforcing the importance of including community perspectives when constructing policy responses.
Multiple focal fatty changes in the liver in patients with porphyria cutanea tarda: A case series and review of the literature
Authors: Takata Kazuhide , Fukunaga Atsushi , Nishizawa Shinya , Uchida Yotaro , Fukuyama Makoto , Nagata Takahiro , Higashi Tomotaka , Fukuda Hiromi , Yamauchi Ryo , Tanaka Takashi , Yokoyama Keiji , Morihara Daisuke , Takeyama Yasuaki , Shakado Satoshi , Sakisaka Shotaro , Hirai Fumihito
Published: December 2021

Porphyria cutanea tarda (PCT) is commonly diagnosed in cases where multiple hyperechoic nodules are observed in the liver. Pathologically, these nodules associated with PCT are focal fatty deposits. We report here, seven cases of PCT with fatty changes over multiple foci in the liver. Furthermore, the characteristics of ultrasonography (US) findings of 32 previously reported cases are summarized. The US features of these nodules showed a homogenous hyperechoic or hyperechoic rim pattern, partial confluence, and no mass effect in the vascular structures. Because multiple hyperechoic liver nodules occasionally mimic malignancies, and because their diagnosis can be challenging, clinicians should consider checking urine porphyrin levels to rule out PCT when such nodules are observed on US.
Imagining the cell therapist: Future CAR T cell monitoring and intervention strategies to improve patient outcomes
Authors: Jain Michael D. , Spiegel Jay Y.
Published: December 2021

Chimeric antigen receptor (CAR) T cell therapy is now approved for the standard of care treatment of several types of relapsed or refractory hematologic malignancies. Future advances may extend cellular therapies to solid tumors or even non‐malignant diseases. As patient need grows, a clinical specialty of “cell therapy” may emerge. Here, we envision the needs of a clinical cell therapist to monitor and intervene upon patients receiving cell therapies. These include: (1) monitoring patient T cell quality and the host immune environment to ensure optimal timing for cell therapy. (2) Tumor antigen profiling to personalize CAR T cell targeting. (3) Real‐time monitoring of CAR T cells and circulating tumor DNA to modulate CAR T cell activity to maximize tumor eradication while mitigating toxicity. (4) Monitoring of CAR rejection and anti‐CAR immunity posttreatment to inform re‐dosing and subsequent cell therapy strategies. Armed with these tools, the future Cell Therapist may optimize and personalize treatment to avoid toxicity and improve efficacy universally across CAR designs.
Risk factors and treatment strategy for clinical hepatico‐jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy: A retrospective study
Authors: Yamaki So , Satoi Sohei , Yamamoto Tomohisa , Hashimoto Daisuke , Hirooka Satoshi , Sakaguchi Tatsuma , Masuda Masataka , Shimatani Masaaki , Ikeura Tsukasa , Sekimoto Mitsugu
Published: December 2021

Backgrounds/Purpose

The purpose of this study was to identify risk factors and establish a treatment strategy for clinical hepatico‐jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy.

Methods

The 443 patients who underwent PD from April 2006 to December 2015 were analyzed. Clinical characteristics were compared between patients with and without clinical HJ stenosis, and risk factors for clinical HJ stenosis were analyzed. In addition, the treatment and clinical course of patients with clinical HJ stenosis were retrospectively reviewed.

Results

Clinical HJ stenosis defined with intrahepatic bile duct dilatation was identified in 40 patients (9.0%). Multivariate analysis revealed that the independent risk factor for clinical HJ stenosis was the hepatic duct at surgery ≤8 mm. Endoscopic HJ stenosis was identified in 36 patients, and 31 patients were treated successfully with double balloon endoscopic retrograde cholangiography; five patients required re‐anastomosis (n = 3) and percutaneous transhepatic biliary drainage (n = 2). Complete obstruction of HJ was found in five patients, and treatment with DB‐ERC was successful in only one patient.

Conclusion

The independent risk factor for clinical HJ stenosis was hepatic duct diameter ≤8 mm. Most cases of endoscopic HJ stenosis were treated successfully with DB‐ERC, except in patients with complete obstruction.
Efficacy and safety of current treatment interventions for patients with severe COVID‐19 infection: A network meta‐analysis of randomized controlled trials
Authors: Cheng Qinglin , Zhao Gang , Chen Junfang , Jia Qingjun , Fang Zijian
Published: December 2021

This study aimed to assess the efficacy and safety of different medications available at present for severe coronavirus disease 2019 (COVID‐19) infection. We searched databases for randomized controlled trials (RCTs) published up to April 30, 2021, with Chinese or English language restriction, of medications recommended for patients (aged 18 years or older) with severe COVID‐19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all‐cause mortality (ACM), and treatment‐emergent adverse events (TEAEs). We identified 1855 abstracts and of these included 15 RCTs comprising 3073 participants through database searches and other sources. In terms of efficacy, compared with the standard of care (SOC) group, no significant decrease in ACM was found in α‐lipoic acid, convalescent plasma (CP), azithromycin, tocilizumab, methylprednisolone, interferon beta, CP/SOC, high dosage sarilumab, low dosage sarilumab, remdesivir, lopinavir–ritonavir, auxora, and placebo group. Compared with placebo, we found that a significant decrease in ACM was only found in methylprednisolone (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.03–0.75]. With respect to TEAEs, the CP group showed lower TEAEs than placebo (OR: 0.07, 95% CI: 0.01–0.58) or SOC (OR: 0.05, 95% CI: 0.01–0.42) group for the therapy of severe COVID‐19 patients. This study only demonstrated that methylprednisolone was superior to placebo in treating patients with severe COVID‐19 infection. Meanwhile, this further confirmed that the safety of other treatment interventions might be inferior to CP for the therapy of severe COVID‐19 patients.
Influence of combined yeast culture and enzymatically hydrolyzed yeast on in vitro ruminal fermentation in contrasting feed substrates
Authors: Sookrali Alisha A , Hughes Martin P
Published: December 2021

BACKGROUND

Feed additives such as live yeast cultures have increasingly been used in ruminant feeds to improve animal performance and feeding efficiency. However, it is not clear how inactive combined yeast cultures affect ruminal gas production, fermentation kinetics and efficiency. Therefore, this study was done to determine the influence of incubating different substrates with a combined yeast culture + enzymatically hydrolyzed yeast (YC + EHY) on in vitro ruminal gas production, fermentation kinetics and metabolizable energy. Six contrasting substrates (Trichantera gigantea and Glircidia sepium leaves, Brachiaria hybrid (cv. Mulato II) leaf + stem and leaf only, Cynodon nlemfuensis and a commercial concentrate dairy feed) were incubated with and without YC + EHY in buffered rumen fluid and gas production measured at 2, 4, 6, 8, 10, 12, 15, 19, 24, 30, 36, 48 and 72 h post incubation.

RESULTS

In vitro fermentation parameters (a, b, a + b and c) were unaffected by YC + EHY except for the lag phase in T. gigantea, which that reduced by 31.3% when it was incubated with YC + EHY. Supplementation with YC + EHY also did not affect metabolizable energy, 72 h organic matter digestibility, 24 h gas or CH4 production within substrate. However, cumulative gas and methane production at peak fermentation in the commercial concentrate feed was reduced by 20% when incubated with YC + EHY.

CONCLUSION

It was concluded that YC + EHY has the potential to improve microbial colonization of T. gigantean substrates and reduce gas and methane production at peak fermentation in commercial concentrate feeds. © 2021 Society of Chemical Industry.
Probing the potential toxicity by characterizing the binding mechanism of sodium dehydroacetate to human serum albumin
Authors: Xu Mengchen , Cui Zhaohao , Xiao Yihua , Liu Changqing , Liu Rutao , Zong Wansong
Published: December 2021

BACKGROUND

Sodium dehydroacetate (DHA‐S) is a common food additive, which can combine with serum proteins in the plasma, but the interaction mechanism between DHA‐S and human serum albumin (HSA) is unclear. In this study, multiple spectroscopy techniques, isothermal titration calorimetry (ITC), molecular docking and esterase activity test were employed to investigate the interaction mechanism of DHA‐S and HSA.

RESULTS

A DHA‐S–HSA complex was formed and the structure of HSA were altered by DHA‐S. Since DHA‐S changed the tight structure of the hydrophobic subdomain IIA where tryptophan (Trp) was placed, the hydrophobicity of the microenvironment of HSA was enhanced. With the addition of DHA‐S, the skeleton structure of HSA became loose and the solvent shell on the HSA surface was destroyed. DHA‐S altered the secondary structure of HSA, resulting in the decreased α‐helix and increased β‐sheet contents. The interaction was exothermic and spontaneous driven by van der Waals and hydrogen bonding. DHA‐S inhibited the esterase activity of HSA. Molecular docking demonstrated that the binding site of DHA‐S on HSA located at the cavity of subdomains IIA and IIIA, but the amino acids related to esterase activity of HSA were not in the binding pocket, indicating that the mechanism by which DHA‐S inhibited HSA esterase activity was the change in protein structure.

CONCLUSION

This study illustrated that DHA‐S interacted with HSA and the structure and function of HSA were affected by DHA‐S. This research could help to understand the toxicity of DHA‐S and provide basic data for safe use of food additives. © 2021 Society of Chemical Industry
Single‐cell RNA Seq reveals cellular landscape‐specific characteristics and potential etiologies for adolescent idiopathic scoliosis
Authors: Yang Yilin , Yang Mingyuan , Shi Dongliang , Chen Kai , Zhao Jian , He Shisheng , Bai Yushu , Shen Pinquan , Ni Haijian
Published: December 2021

Backgrounds

Abnormal vertebral growth and development have been found in adolescent idiopathic scoliosis (AIS) patients, and the proliferation and differentiation of bone development‐related cells play important roles in its pathogenesis. However, a comprehensive single‐cell‐level differentiation roadmap in AIS has not been achieved.

Methods

The present study compared the single‐cell level cellular landscapes of spinal cancellous bone tissues between AIS patients and healthy subjects using high throughput single‐cell RNA sequencing (scRNA‐seq), which covers multiple cellular lineages including osteoblast, chondrocyte, osteoclast and related immunocytes. We constructed the differentiation trajectories of bone development‐related cell lineages through pseudotime analysis, and the intercellular‐communication networks between bone development‐related cells and immunocytes were further developed.

Results

A total of 11 distinct cell clusters were identified according to the genome‐wide transcriptome profiles. t‐Distributed stochastic neighbor embedding (t‐SNE) analysis showed that mesenchymal stem cells (MSC) were classified into three subtypes: MSC‐LOXL2, MSC‐IGFBP5, and MSC‐GJA1. Gene ontology (GO) analysis showed that MSC‐GJA1 might possess greater osteoblast differentiation potential than the others. MSC‐IGFBP5 was the specific MSC subtype observed only in AIS. There were two distinct gene expression clusters: OB‐DPT and OB‐OLFML2B, and the counts of osteoblasts derived from AIS was significantly less than that of non‐AIS subjects. In AIS patients, MSC‐IGFBP5 failed to differentiate into osteoblasts and exhibited negative regulation of cell proliferation and enhanced cell death. CPC‐PCNA was found to be the specific chondrocyte progenitor cell (CPC) subtype observed only in AIS patients. The cell counts of OC‐BIRC3 in AIS were less than those in controls. Pseudotime analysis suggested two possible distinct osteoclast differentiation patterns in AIS and control subjects. Monocytes in AIS mainly differentiated into OC‐CRISP3.

Conclusions

Our single‐cell analysis first revealed differences existed in the cellular states between AIS patients and healthy subjects and found the differentiation disruption of specific MSC and CPC clusters in AIS. Cell communication analysis provided the possible pathogenesis of osteoblast and chondrocyte differentiation dysfunction in AIS.
Effects of aquatic therapy on people with osteopenia or osteoporosis: A systematic review
Authors: Arias Avila Mariana , Regina Mendes da Silva Serrão Paula , Bernardi dos Santos Gabriel , Garcia Godoy Amanda , dos Santos Sousa Ana Jéssica , Driusso Patricia
Published: December 2021

Background

Aquatic exercises have been widely used to treat people with osteopenia and osteoporosis (OP), claiming that they may improve balance; nonetheless, there is still controversy on its use for this population.

Objectives

To investigate the effects of aquatic exercise (AE) on people with osteopenia or OP.

Methods

Systematic review that included clinical trials, with at least one AE group and a control group. The electronic databases PubMed, EMBASE, Cochrane, Scopus and Web of Science were searched. The risk of bias assessment was performed independently by two reviewers with the Revised Cochrane risk‐of‐bias tool for randomized trials (RoB 2).

Results

A total of 1793 articles were identified, and 7 articles were considered eligible, mostly considered as of low risk of bias. The total sample size was composed of 562 women (mean ages between 58.6 ± 6.7 and 73.3 ± 3.9). The interventions were supplementation, pharmacological treatment and protocols both of land‐based exercises (LE) and AE. Outcomes were quality of life, functionality, balance, function, mobility, handgrip, lower limbs and trunk strength, flexibility and pain, with controversial results on all variables.

Conclusions

Even though AE seem to be beneficial for people with osteopenia or OP, protocols for evaluation and treatment are heterogeneous and did not allow a meta‐analysis computation. As such, it was not possible to conclude if AE are beneficial to people with osteopenia or OP.

Trial Registration

This systematic review was registered in the international prospective register of systematic reviews (PROSPERO [OMITTED FOR BLINDING PURPOSES]).
Toward Adequate Food Systems: Collaboration and “Nonsovereign” Food Futures
Authors: Garth Hanna
Published: December 2021

Since at least the end of World War II, there have been efforts on a global scale to reduce food insecurity through neoliberal, industrial, and technocratic solutions often led by multinational organizations and corporations. These programs have been critiqued for causing environmental degradation, undermining local economies and food production systems, and failing to account for historically and culturally relevant local food preferences. Food sovereignty has been introduced as an alternative approach to food security; it is focused on historically and culturally relevant food needs and returning to more sustainable local food production that is better suited to the environment. Based on over a decade of fieldwork in both Santiago de Cuba and Los Angeles, in this article I detail the ways in which these solutions to food insecurity fall short of what is necessary to ameliorate the failures of our food systems. I analyze the tensions between the needs for a food system that supplies sufficient quantities versus food systems that adequately address local needs for historically and culturally appropriate foods that are produced and distributed in ways that are environmentally sustainable and support local economies. Drawing on the Los Angeles Food Policy Council’s Good Food Purchasing Program as a case study, I offer the possibility of a “nonsovereign cooperative approach” to establishing, recreating, or maintaining adequate food systems that serve various needs of local people within the contemporary global food system.
Time to Move on From Measuring Chlorine Residuals With Outdated Methods
Authors: Deem Steve , Feagin Nancy , Chavez Krista
Published: December 2021

Is it time to move on from using test strips and color wheels to monitor chlorine residuals? In the State of Washington, different residual test methods produced different results for the same sampled water, casting the reliability of traditional approaches into question.
Safety: Take a Threefold Approach to Create an Inclusive Workplace
Authors: Williams Hayley W.
Published: December 2021

When the topic of safety comes up in the workplace, the focus tends to be on physical safety. Psychological and emotional safety are equally important, and implementing policies that promote all of these to create an inclusive workplace benefits employees and water utilities.
Comparing LASSO and random forest models for predicting neurological dysfunction among fluoroquinolone users
Authors: Ellis Darcy E. , Hubbard Rebecca A. , Willis Allison W. , Zuppa Athena F. , Zaoutis Theoklis E. , Hennessy Sean
Published: December 2021

Background

Fluoroquinolones are associated with central (CNS) and peripheral (PNS) nervous system symptoms, and predicting the risk of these outcomes may have important clinical implications. Both LASSO and random forest are appealing modeling methods, yet it is not clear which method performs better for clinical risk prediction.

Purpose

To compare models developed using LASSO versus random forest for predicting neurological dysfunction among fluoroquinolone users.

Methods

We developed and validated risk prediction models using claims data from a commercially insured population. The study cohort included adults dispensed an oral fluoroquinolone, and outcomes were CNS and PNS dysfunction. Model predictors included demographic variables, comorbidities and medications known to be associated with neurological symptoms, and several healthcare utilization predictors. We assessed the accuracy and calibration of these models using measures including AUC, calibration curves, and Brier scores.

Results

The underlying cohort contained 16 533 (1.18%) individuals with CNS dysfunction and 46 995 (3.34%) individuals with PNS dysfunction during 120 days of follow‐up. For CNS dysfunction, LASSO had an AUC of 0.81 (95% CI: 0.80, 0.82), while random forest had an AUC of 0.80 (95% CI: 0.80, 0.81). For PNS dysfunction, LASSO had an AUC of 0.75 (95% CI: 0.74, 0.76) versus an AUC of 0.73 (95% CI: 0.73, 0.74) for random forest. Both LASSO models had better calibration, with Brier scores 0.17 (LASSO) versus 0.20 (random forest) for CNS dysfunction and 0.20 (LASSO) versus 0.25 (random forest) for PNS dysfunction.

Conclusions

LASSO outperformed random forest in predicting CNS and PNS dysfunction among fluoroquinolone users, and should be considered for modeling when the cohort is modest in size, when the number of model predictors is modest, and when predictors are primarily binary.