bluuebunny/crossref_metadata_2025 huggingface dataset:
A cohort-based nutrition ECHO for community health workers
Authors: T. Thomas Karmella , Friedman Sarah A , J. Larson Madalyn , C. Jorgensen Troy , Sharma Sneha , Smith Amie , S. Lavi Mordechai
Published: January 2023

Project Extension for Community Healthcare Outcomes (ECHO) Nevada applied the ECHO virtual hub-and-spoke telementoring model over nine 6-week cohorts (between November 2019 and November 2021) supporting community health workers (CHWs) who advise clients with diabetes or pre-diabetes. This study describes the program implementation, including evaluation data collection efforts. Didactic topics included ‘Intro to Healthy Eating and Easy Wins’ to ‘Grocery Shopping, Cooking Tips, Reading Labels, Meal Plans’ and ‘Reducing Bias and Being a Good Role Model’. Spoke participants signed up to review cases. Seventy-three of the enrolled participants (n = 100) attended three or more of the six sessions. Spoke participants completed 42 case presentations. The average self-efficacy increased from 2.7 [standard deviation (SD): 1.1] before completing the program to 4.1 (SD: 0.8) after completing the program. Average knowledge scores increased from 71 (SD: 16) before completing the program to 83 (SD: 14) after completing the program. Five group interviews drew actionable feedback that was incorporated into the program. Key elements of the ECHO model were successfully incorporated to support educational goals of a cohort of CHWs in nutritional coaching. Our program evaluation data tracking system shows non-significant but encouraging results regarding self-efficacy improvement and knowledge retention.
Predicting brain-regional gene regulatory networks from multi-omics for Alzheimer’s disease phenotypes and Covid-19 severity
Authors: Khullar Saniya , Wang Daifeng
Published: January 2023

Neuroinflammation and immune dysregulation play a key role in Alzheimer’s disease (AD) and are also associated with severe Covid-19 and neurological symptoms. Also, genome-wide association studies found many risk single nucleotide polymorphisms (SNPs) for AD and Covid-19. However, our understanding of underlying gene regulatory mechanisms from risk SNPs to AD, Covid-19 and phenotypes is still limited. To this end, we performed an integrative multi-omics analysis to predict gene regulatory networks for major brain regions from population data in AD. Our networks linked transcription factors (TFs) to TF binding sites (TFBSs) on regulatory elements to target genes. Comparative network analyses revealed cross-region-conserved and region-specific regulatory networks, in which many immunological genes are present. Furthermore, we identified a list of AD–Covid genes using our networks involving known and Covid-19 genes. Our machine learning analysis prioritized 36 AD–Covid candidate genes for predicting Covid severity. Our independent validation analyses found that these genes outperform known genes for classifying Covid-19 severity and AD. Finally, we mapped genome-wide association study SNPs of AD and severe Covid that interrupt TFBSs on our regulatory networks, revealing potential mechanistic insights of those disease risk variants. Our analyses and results are open-source available, providing an AD–Covid functional genomic resource at the brain region level.
Are heat-killed probiotics more effective than live ones on colon length shortness, disease activity index, and the histological score of an inflammatory bowel disease-induced murine model? A meta-analysis
Authors: Poaty Ditengou Junior Isaac Celestin , Ahn Sung-Il , Chae Byungho , Choi Nag-Jin
Published: January 2023

This study was conducted to compare the efficiency of heat-killed and live probiotics against colon length shortness, disease activity index (DAI), and the histological score of an inflammatory bowel disease (IBD) via a meta-analysis. In February 2022, the eligible papers were collected from four databases (Google Scholar, PubMed, ScienceDirect, and Scopus). Using common- and random-effects models, the effect sizes were estimated throughout the standardized mean difference. Forty-three papers were recorded for our meta-analysis, and the heterogeneity of the effect sizes was determined with Cochran’s Q test, followed by meta-ANOVA and meta-regression analyses. The probiotics (live and heat-killed) had globally an improving or preventive effect on colon length shortness, DAI, and histological score. The sub-group analysis revealed that the heat-killed probiotics had statistically (P > .05) the same improving effect on colon length shortness, DAI, and histological score as live probiotics. In conclusion, this study suggested that live and heat-killed probiotics had a similar impact on IBD symptoms investigated in this study. The present outcomes would be a good base for researchers willing to further compare the effects of live and heat-killed probiotics on IBD.
Prognostic awareness in Japanese patients with advanced cancer: a follow-up cohort study
Authors: Hiratsuka Yusuke , Oishi Takayuki , Miyashita Mitsunori , Morita Tatsuya , Mack Jennifer W , Imai Hiroo , Mori Takahiro , Sakayori Masato , Mori Masanori , Maeda Isseki , Hamano Jun , Ishioka Chikashi , Inoue Akira
Published: January 2023

Background

Patients with advanced cancer have been reported to be more likely to receive goal-concordant care if they have accurate prognostic awareness. However, many patients do not have this awareness. This study aimed to examine the prognostic awareness among Japanese patients with advanced cancer.

Methods

This single-center, follow-up cohort study included Japanese patients with advanced cancer who received chemotherapy at Tohoku University Hospital between January 2015 and January 2016. Patients were surveyed at enrollment and followed up for clinical events for 5 years thereafter. We compared (i) the patients’ prognostic awareness with both actual survival time and physician’s prediction of survival and (ii) physician’s prediction of survival time with actual survival. Factors associated with accurate prognostic awareness were identified by univariate analysis.

Results

Of the 133 patients eligible for the study, 57 patients were analyzed. Only 10 (17.5%) patients had accurate prognostic awareness. Forty-three patients (75.4%) were optimistic about their prognosis; >80% of patients were more optimistic than their physicians about their prognosis. The physicians’ predictions were accurate in for patients (37.5%). Accurate prognostic awareness was associated with physician’s explanation of the prognosis and patients’ perception of a good death.

Conclusions

A majority of the patients with advanced cancer in this study had prognostic awareness that was more optimistic in comparison with their actual survival, and most were more optimistic than their physicians about their prognosis. Further research is needed to develop programs to facilitate the discussion of life expectancy with patients in a manner that is consistent with their preferences.
Integration of chromatin accessibility and gene expression reveals new regulators of cold hardening to enhance freezing tolerance inPrunus mume
Authors: Li Ping , Zheng Tangchun , Li Lulu , Liu Weichao , Qiu Like , Ahmad Sagheer , Wang Jia , Cheng Tangren , Zhang Qixiang
Published: January 2023

Low temperature is one of the most important abiotic factors limiting the growth, development and geographical distribution of plants. Prunus mume is an attractive woody ornamental plant that blooms in early spring in Beijing. However, the molecular mechanisms underlying cold hardening to enhance freezing tolerance in Prunus genus remains elusive. This study examined the dynamic physiological responses induced by cold hardening, and identified freezing-tolerance genes by RNA-seq and ATAC-seq analyses. Cold hardening elevated the content of soluble substances and enhanced freezing resistance in P. mume. Transcriptome analysis indicated that the candidate differentially expressed genes (DEGs) were those enriched in Ca2+ signalling, mitogen-activated protein kinase (MAPK) cascade, abscisic acid signalling, and inducer of CBF expression 1 (ICE)-C-repeat binding factor (CBF) signalling pathways. The openness of gene chromatin positively correlated with the expression level of these genes. Thirteen motifs were identified in the open chromatin regions in the treatment group subjected to freezing after cold hardening. The chromatin opening of transcription start site at the proximal –177 region of cold-shock protein CS120-like (PmCSL) was markedly increased, while the expression level of PmCSL was significantly up-regulated. Overexpression of PmCSL in Arabidopsis significantly improved the freezing tolerance of transgenic plants. These findings provide new insights into the regulatory mechanism of freezing tolerance to improve breeding of cold-hardy P. mume plants.
Tracing of persistent Listeria monocytogenes contamination in ewe’s milk farm
Authors: Minarovičová Jana , Adriana Véghová , Zuzana Kubicová , Andrezál Michal , Hana Drahovská , Eva Kaclíková
Published: January 2023

Ewe’s milk farm production is permanently associated with the risk of contamination by pathogenic bacteria, including Listeria monocytogenes. In the present study, the prevalence and diversity of L. monocytogenes strains repeatedly isolated from tank ewe’s milk and the milking environment on a farm in Slovakia during a prolonged period were investigated to identify the source of potentially persistent contamination. A total of 140 samples along the milk production chain were collected during an 18-month period. From all these samples, 45 samples were found L. monocytogenes positive with 90.3% positivity of tank milk samples (28 positive samples from 31 analysed). Pulsed-field gel electrophoresis profiling resulted in strain discrimination into six profiles with one pulsotype (NS1) corresponding to MLST-ST14 being predominant. A total of 17 proportionally selected L. monocytogenes isolates, including 11 NS1/ST14 isolates, were subjected to whole genome sequencing. Resulted data were used to compare the genomes diversity and to confirm the persistent contamination when <10 allelic differences threshold in cgMLST analysis was applied. The source of persistent contamination was localized inside the milking apparatus, probably in shelters that were very difficult to clean. Despite great efforts, the ewe’s milk contamination could not be eliminated during the reporting period.
Potential role of rumen bacteria in modulating milk production and composition of admixed dairy cows
Authors: Lilian Musembei , Rawlynce Bett , Charles Gachuiri , Felix Kibegwa
Published: January 2023

Cattle milk is an important food for the growing calf and humans because of its concentrated macro and micro nutrients. However, the quantity and quality of milk nutrients vary depending on several factors. This study evaluated the effect of dietary modification on rumen bacteria as well as the potential role of rumen bacteria in modifying milk production and composition profile. Using a 16S rRNA metagenomic approach, the study characterized the rumen bacterial community composition in four dairy cows and their milk production and composition. The results indicated that Bacteroidetes and Firmicutes were the dominant bacteria, totaling ∼83.7% of the rumen bacteria. An increase in concentrate proportion in diet led to an increase in the abundance of Bacteroidetes (P ≤ 0.05) and Proteobacteria while Firmicutes and Fibrobacter decreased. Milk production and composition were highly correlated with the abundance of various rumen bacterial members. Lentispaerae (P = 0.010), and Synergistetes (P = 0.011) exhibited a positive and significant correlation while Tenericutes (P = 0.009) showed a negative correlation with milk protein. Fusobacteria (P = 0.016) showed a negative correlation with milk lactose. Similarly, several genera showed correlations with milk parameters. The correlation between microbes with milk parameters implies that the bacterial community possesses the potential to influence milk production and composition.
What gets categorized counts: Controlled vocabularies, digital affordances, and the international digital humanities conference
Authors: Guiliano Jennifer , Estill Laura
Published: January 2023

This article explores how terms are incorporated into the conference submission and review process for the international digital humanities conference. This article provides an overview of the Alliance for Digital Humanities Organizations (ADHO) conference reviewing process and how the controlled vocabulary structures the review process. We show how expanding and rethinking the controlled vocabulary can impact the experience of those who submit, review, and attend the conference. We consider how ConfTool, the submission and reviewing portal used for the international digital humanities conference, processes the controlled vocabulary and algorithmically influences the review of submissions. Ultimately, we advocate for the ability to make intentional and careful changes to conference vocabularies including considering the adoption of a formal ontology. We also suggest that changes to the ConfTool algorithm are needed to ensure a diverse and equitable future for digital humanities.
Ageing and quenching through the ageing diagram: predictions from simulations and observational constraints
Authors: Corcho-Caballero Pablo , Ascasibar Yago , Sánchez Sebastián F , López-Sánchez Ángel R
Published: January 2023

We study recent changes on the star-formation history (SFH) of galaxies by means of the ageing diagram (AD), tracing the fraction of stars formed during the last ∼20 Myr through the equivalent width of the $\rm H\alpha$ line and ∼1−3 Gyr through the dust-corrected optical colour (g − r)0or the Balmer break. We provide a physical characterization by using Pipe3Destimates of the SFH of Calar Alto Legacy Integral Field Area and Mapping Nearby Galaxies at Apache Point Observatory galaxies, in combination with the predictions from IllustrisTNG-100. Our results show that the AD may be divided into four domains that correlate with the stellar mass fractions formed in the last 20 Myr and 3 Gyr: ageing systems, whose star formation rate changes on scales of several Gyr, account for $70-80{{\ \rm per\ cent}}$ of the galaxy population. Objects whose SFH was abruptly truncated in the last ∼1 Gyr arrange along a detached quenched sequence that represents $\sim 5-10{{\ \rm per\ cent}}$ by (volume-corrected) number for 109 < M*/M⊙ < 1012. Undetermined systems represent an intermediate population between the ageing and quenched regimes. Finally, Retired galaxies, dominated by old stellar populations, are located at the region in the AD where the ageing and quenched sequences converge. Defining different star formation activity levels in terms of the birth rate parameter $b\equiv \frac{SFR}{\langle SFR \rangle }$, we find that galaxies transit from the ageing to quenched sequences on scales ∼500 Myr. We conclude that the AD provides a useful tool to discern recently quenched galaxies from the dominant ageing population.
Physiological effects of yerba maté (Ilex paraguariensis): a systematic review
Authors: José Manuela F B , Machado Roberta P , Araujo Pablo A B , Speretta Guilherme F
Published: January 2023

Context

Clinical studies have found an association between yerba maté intake and beneficial physiological effects. Nevertheless, no systematic reviews have been conducted to shed light on the data supporting this association.

Objective

The present systematic review aimed to investigate the physiological effects of yerba maté.

Data Sources

Searches were performed in 6 databases (Embase, LILACS, Scopus, PubMed, SciELO, Web of Science) and 3 grey literature databases (OpenGrey, ProQuest, Google Scholar). Relevant publications were identified, and the reference lists of included studies were searched manually for randomized clinical trials, nonrandomized clinical trials, and observational studies investigating the physiological effects of yerba maté.

Data Extraction

Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials and the Cochrane ROBINS-I (Risk Of Bias In Nonrandomized Studies of Interventions) tool. Joanna Briggs Institute critical appraisal tools were used for cross-sectional, case series, cohort, and case-control studies. The overall certainty of the evidence was estimated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) working group summary of findings table.

Data Analysis

Of 1096 studies identified, 32 were included. Studies showed consistent effects of yerba maté intake on metabolism improvement and antioxidant and anti-inflammatory activities in different populations. Benefits for body weight and composition, exercise performance, mood, and appetite, in addition cardio- and neuroprotective effects, were also observed. Risk of bias was categorized as high in 22 studies, moderate in 9 studies, and low in 1 study. The certainty of evidence ranged from moderate to very low.

Conclusion

The available literature indicates that yerba maté can be used within a balanced and healthy diet for prevention and adjuvant treatment of chronic diseases.

Systematic Review Registration

PROSPERO registration number CRD42020200196.
Countering the Fiction of Neutrality: Pushing for Transparency?
Authors: Van de Graaf Cathérine , Nußberger Angelika
Published: January 2023

Many scholars accept that the principle of neutrality is to a large extent a fictional concept. They often propose different variations that would better realize its prescribed aim of equality. In this contribution, we argue that state agents in general, and judges in particular, cannot be ‘neutral’ as they are not abstract entities. They do not enter the judiciary with a clean slate but as persons subjected to a myriad of formative experiences, connected to their worldview, gender, nationality, socio-economic background, and so on. Thus, the fiction of neutrality of the State is inevitably linked with a lack of transparency: not showing religious, atheist, or agnostic as well as political convictions is not the same as not having them. An alternative model would be to emphasize transparency, but simultaneously strive for diversity of different convictions represented on the Bench. Such a system would prompt self-conscious reflection on the role of worldviews in the judging process. It would, however, create new dilemmas as it would be impossible to reach an adequate equilibrium and thus undermine the confidence in the judiciary.
Clinical Treatment Guidelines for Tafasitamab plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Nedved Adrienne , Maddocks Kami , Nowakowski Grzegorz S
Published: January 2023

Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 24% of new cases of B-cell non-Hodgkin lymphoma in the US each year. Up to 50% of patients relapse or are refractory (R/R) to the standard first-line treatment option, R-CHOP. The anti-CD19 monoclonal antibody tafasitamab, in combination with lenalidomide (LEN), is an NCCN preferred regimen for transplant-ineligible patients with R/R DLBCL and received accelerated approval in the US (July 2020) and conditional marketing authorization in Europe (August 2021) and other countries, based on data from the L-MIND study. The recommended dose of tafasitamab is 12 mg/kg by intravenous infusion, administered in combination with LEN 25 mg for 12 cycles, followed by tafasitamab monotherapy until disease progression or unacceptable toxicity. Tafasitamab + LEN is associated with durable responses in patients with R/R DLBCL. The majority of clinically significant treatment-associated adverse events are attributable to LEN and can be managed with dose modification and supportive therapy. We provide guidelines for the management of patients with R/R DLBCL treated with tafasitamab and LEN in routine clinical practice, including elderly patients and those with renal and hepatic impairment, and advice regarding patient education as part of a comprehensive patient engagement plan. Our recommendations include LEN administration at a reduced dose if required in patients unable to tolerate the recommended dose. No dose modification is required for tafasitamab in special patient populations.
Church
Authors: Day Abby
Published: January 2023

This chapter reviews one of the most common explanations the Boomers gave about their earlier church-going pattern: ‘It was a social thing’. In their childhoods the church was a social community to which their families belonged, both for social contact and to meet society’s wider expectations about an important mode of ‘respectability’. Boomers did not generally experience religious practices in their homes or have a sense of being close to God or Jesus during their childhood years: the church was a place to meet friends and family, not commune with anything more ‘spiritual’. The common, mid-twentieth-century practice of segregating children and adults through a Sunday School appears to have had the unintended consequence of diminishing any sense of religiosity or spirituality.
Creating a Seamless Organization
Authors: Kanore Lalit , Masatkar Priti
Published: January 2023

The case study is a typical representative of majority of the family managed large groups of industries engaged in manufacturing marketing and trading activity through several of their group companies. The case represents major issues faced by the generational and successional chiefs as heirs to the traditional businesses of group companies in their major tasks of further steering of the group companies through the turn around and transformational changes compelled by the major disruptions due to technology, trade restrictions in international businesses, and compliance to several regulatory norms towards climate change and pollution control along with sustainability standards. It is a real churn that these new generational chiefs have to manage to sustain and grow their businesses.
Sony Pictures Network— A New PMA Philosophy
Authors: Praveen Roopa , Aher Dilip , Anute Nilesh
Published: January 2023

Sony Pictures Networks India (SPN has several channels including Sony Entertainment Television SET and SET HD), one of India’s leading Hindi general entertainment television channels. SPN reaches out to over 700 million viewers in India and is available in 167 countries. The PESTEL/PESTLE analysis of Sony Corporation reveals a number of significant opportunities and threats that shape the electronics, gaming, entertainment, and financial services markets. As part of its talent development program schedules, SPN are also upskilling their current employees by providing alternate learning experiences, reverse mentoring, expert talks, and design thinking workshops, among other initiatives. The HR policies at Sony is employee inclusive, however due to the growing workforce there have been certain management changes that Sony has had to incorporate. This case delves into the management style of Sony for its employees and analyses the best practices.
Employee Unrest and the Role of Labour Unions
Authors: Parab Varsha , Mahadik Ramesh , Tripathi Diksha
Published: January 2023

In 1970s when industrial revolution was at its boom in India, four engineers started manufacturing of Stainless steel and Mild steel for pharmaceutical, chemical, fertilisers, and many other companies. The chaos started in 1978 due to financial crisis in the organization, the two labour unions and their demands is the central character of the case. The case throws light on how due to leadership issues, the management of the company always takes the benefit of different leaders by keeping a different relationship with two different leaders. Almost two decades due to disputes between two union companies could not give principal benefits to the employee as they demanded at the beginning of the company’s establishment. The case discusses on various laws provided to safeguard employee benefits by the state. It narrates the benefit and struggle of employees in SME’s.
Do not panic: An intron-centric guide to alternative splicing
Authors: Petrillo Ezequiel
Published: January 2023

This review is an attempt to establish concepts of splicing and alternative splicing giving proper relevance to introns, the key actors in this mechanism. It might also work as a guide for those who found their favorite gene undergoes alternative splicing and could benefit from gaining a theoretical framework to understand the possible impacts of this process. This is not a thorough review of all the work in the field, but rather a critical review of some of the most relevant work done to understand the underlying mechanisms of splicing and the key questions that remain unanswered such as: What is the physiological relevance of alternative splicing? What are the functions of the different outcomes? To what extent do different alternative splicing types contribute to the proteome? Intron retention is the most frequent alternative splicing event in plants and, although scientifically neglected, it is also common in animals. This is a heterogeneous type of alternative splicing that includes different sub-types with features that have distinctive consequences in the resulting transcripts. Remarkably, intron retention can be a dead end for a transcript, but it could also be a stable intermediate whose processing is resumed upon a particular signal or change in the cell status. New sequencing technologies combined with the study of intron lariats in different conditions might help to answer key questions and could help us to understand the actual relevance of introns in gene expression regulation.
One-helix protein 2 is not required for the synthesis of photosystem II subunit D1 in Chlamydomonas
Authors: Wang Fei , Dischinger Korbinian , Westrich Lisa Désirée , Meindl Irene , Egidi Felix , Trösch Raphael , Sommer Frederik , Johnson Xenie , Schroda Michael , Nickelsen Joerg , Willmund Felix , Vallon Olivier , Bohne Alexandra-Viola
Published: January 2023

In land plants and cyanobacteria, co-translational association of chlorophyll (Chl) to the nascent D1 polypeptide, a reaction center protein of photosystem II (PSII), requires a Chl binding complex consisting of a short-chain dehydrogenase (high chlorophyll fluorescence 244 [HCF244]/uncharacterized protein 39 [Ycf39]) and one-helix proteins (OHP1 and OHP2 in chloroplasts) of the light-harvesting antenna complex superfamily. Here, we show that an ohp2 mutant of the green alga Chlamydomonas (Chlamydomonas reinhardtii) fails to accumulate core PSII subunits, in particular D1 (encoded by the psbA mRNA). Extragenic suppressors arose at high frequency, suggesting the existence of another route for Chl association to PSII. The ohp2 mutant was complemented by the Arabidopsis (Arabidopsis thaliana) ortholog. In contrast to land plants, where psbA translation is prevented in the absence of OHP2, ribosome profiling experiments showed that the Chlamydomonas mutant translates the psbA transcript over its full length. Pulse labeling suggested that D1 is degraded during or immediately after translation. The translation of other PSII subunits was affected by assembly-controlled translational regulation. Proteomics showed that HCF244, a translation factor which associates with and is stabilized by OHP2 in land plants, still partly accumulates in the Chlamydomonas ohp2 mutant, explaining the persistence of psbA translation. Several Chl biosynthesis enzymes overaccumulate in the mutant membranes. Partial inactivation of a D1-degrading protease restored a low level of PSII activity in an ohp2 background, but not photoautotrophy. Taken together, our data suggest that OHP2 is not required for psbA translation in Chlamydomonas, but is necessary for D1 stabilization.
Determination and characterization of patient subgroups based on pain trajectories in hand osteoarthritis
Authors: van der Meulen Coen , van de Stadt Lotte A , Rosendaal Frits R , Runhaar Jos , Kloppenburg Margreet
Published: January 2023

Objectives

To investigate pain, pain trajectories and their determinants in hand osteoarthritis (OA).

Methods

Data from the HOSTAS (Hand OSTeoArthritis in Secondary care) consisting of consecutive hand OA patients were used. Australian Canadian Osteoarthritis Hand Index (AUSCAN) pain was measured yearly for four years. Patients with complete AUSCAN at ≥2 time points were eligible for longitudinal analysis. Associations between variables of interest and baseline AUSCAN pain were investigated with linear regression. Development of pain over time was modelled using latent class growth analysis (LCGA). Associations of LCGA classes with variables of interest were analysed using multinomial logistic regression adjusted for baseline pain.

Results

A total of 484/538 patients [mean (s.d.) age 60.8 (8.5) years, 86% women, mean (s.d.) AUSCAN pain 9.3 (4.3)] were eligible for longitudinal analysis. Sex, marital and working status, education, disease duration and severity, anxiety and depression scores, lower health-related quality of life (HR-QoL), specific illness perceptions and coping styles were associated with baseline pain. LCGA yielded three classes, characterized by average pain levels at baseline; average pain remained stable over time within classes. Classes with more pain were positively associated with BMI, tender joint count, symptom duration, hand function scores and depression scores, negatively with physical HR-QoL, and education level.

Conclusion

Baseline pain was associated with patient and disease characteristics, and psychosocial factors. LCGA showed three pain trajectories in hand OA patients, with different baseline pain levels and stable pain over time. Classes were distinguished by BMI, education level, disease severity, depression and HR-QoL.
Rehabilitative Training Enhances Therapeutic Effect of Human iPSC-Derived Neural Stem/Progenitor Cells Transplantation in Chronic Spinal Cord Injury
Authors: Shibata Takahiro , Tashiro Syoichi , Shibata Shinsuke , Shinozaki Munehisa , Shindo Tomoko , Hashimoto Shogo , Kawai Momotaro , Kitagawa Takahiro , Ago Kentaro , Matsumoto Morio , Nakamura Masaya , Okano Hideyuki , Nagoshi Narihito
Published: January 2023

Cell transplantation therapy using human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a new therapeutic strategy for spinal cord injury (SCI). Preclinical studies have demonstrated the efficacy of hiPSC-NS/PCs transplantation in the subacute phase of SCI. However, locomotor recovery secondary to hiPSC-NS/PCs transplantation is limited in the chronic phase, suggesting that additional treatment, including rehabilitative training, is required to ensure recovery. The therapeutic potential of hiPSC-NS/PCs that qualify for clinical application is yet to be fully delineated. Therefore, in this study, we investigated the therapeutic effect of the combined therapy of clinical-grade hiPSC-NS/PCs transplantation and rehabilitative training that could produce synergistic effects in a rodent model of chronic SCI. Our findings indicated that rehabilitative training promoted the survival rate and neuronal differentiation of transplanted hiPSC-NS/PCs. The combination therapy was able to enhance the expressions of the BDNF and NT-3 proteins in the spinal cord tissue. Moreover, rehabilitation promoted neuronal activity and increased 5-HT-positive fibers at the lumbar enlargement. Consequently, the combination therapy significantly improved motor functions. The findings of this study suggest that the combined therapy of hiPSC-NS/PCs transplantation and rehabilitative training has the potential to promote functional recovery even when initiated during chronic SCI.
Protein Kinase C Modulation Determines the Mesoderm/Extraembryonic Fate Under BMP4 Induction From Human Pluripotent Stem Cells
Authors: Godoy-Parejo Carlos , Deng Chunhao , Xu Jiaqi , Zhang Zhaoying , Ren Zhili , Ai Nana , Liu Weiwei , Ge Wei , Deng Chuxia , Xu Xiaoling , Chin Y Eugene , Chen Guokai
Published: January 2023

The interplay among mitogenic signaling pathways is crucial for proper embryogenesis. These pathways collaboratively act through intracellular master regulators to determine specific cell fates. Identifying the master regulators is critical to understanding embryogenesis and to developing new applications of pluripotent stem cells. In this report, we demonstrate protein kinase C (PKC) as an intrinsic master switch between embryonic and extraembryonic cell fates in the differentiation of human pluripotent stem cells (hPSCs). PKCs are essential to induce the extraembryonic lineage downstream of BMP4 and other mitogenic modulators. PKC-alpha (PKCα) suppresses BMP4-induced mesoderm differentiation, and PKC-delta (PKCδ) is required for trophoblast cell fate. PKC activation overrides mesoderm induction conditions and leads to extraembryonic fate. In contrast, PKC inhibition leads to β-catenin (CTNNB1) activation, switching cell fate from trophoblast to mesoderm lineages. This study establishes PKC as a signaling boundary directing the segregation of extraembryonic and embryonic lineages. The manipulation of intrinsic PKC activity could greatly enhance cell differentiation under mitogenic regulation in stem cell applications.
Undetected Fetal Growth Restriction During the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Zafman Kelly B. , Cudjoe Efe , Levine Lisa D. , Srinivas Sindhu K. , Schwartz Nadav
Published: January 2023

This was a retrospective cohort study of patients who delivered singleton, small-for-gestational-age (SGA) neonates between April and June 2019, before the coronavirus disease 2019 (COVID-19) pandemic (pre–COVID-19), and between April and July 2020, during the pandemic (COVID-19 epoch). The primary outcome was the rate of undetected antenatal fetal growth restriction (FGR) in the two periods. A total of 268 patients met inclusion criteria. Patients who delivered small-for-gestational-age neonates during the COVID-19 epoch were significantly more likely to have undetected FGR compared with those who delivered pre–COVID-19 (70.1% vs 58.1%, P=.04). Patients who delivered SGA neonates during the COVID-19 epoch had more telehealth visits but fewer in-person prenatal visits, recorded fundal height measurements, and growth ultrasonograms. As telemedicine continues to be incorporated into prenatal care, these data may lend further support toward self-assessment of fundal height or routine third-trimester growth ultrasonograms to identify fetal growth abnormalities.
The Evolution of Iron-Related Comorbidities and Hospitalization in Patients with Hemochromatosis: An Analysis of the Nationwide Inpatient Sample
Authors: Abou Yassine Ahmad , MacDougall Kira , Sasso Roula , Shammaa Youssef , Alsheikh Mira , Abureesh Mohammad , Dahabra Loai , Alshami Mohammad , Mulrooney Stephen
Published: January 2023

Hemochromatosis, either hereditary hemochromatosis (HH) or secondary hemochromatosis, consists of the accumulation of iron in the liver, heart, and other organs. It leads to end-organ damage in a proportion of affected subjects. Although liver-related morbidity (cirrhosis and hepatocellular carcinoma [HCC]) and mortality are well established, the frequency of these complications remains controversial. The aim of this study is to examine the rate of hospitalization and the incidence of iron overload-related comorbidities in patients with hemochromatosis between the years of 2002 and 2010. We queried the Nationwide Inpatient Sample (NIS) database from the year 2002 to 2010. We included adults (age ≥18 years) and used the ICD-CM 9 code 275.0x to identify hospitalized patients with a diagnosis of hemochromatosis. Data analysis for this study was generated using SAS software version 9.4. A total of 168,614 hospitalized patients between 2002 and 2010 had a diagnosis of hemochromatosis. The majority were males (57%) with a median age of 54 years (37–68), with a predominance of white patients (63.3%) followed by black (26.8%). The rate of hospitalization among patients with hemochromatosis increased by 79% between the years 2002 and 2010 (34.5/100,000 in 2002 vs 61.4/100,000 in 2010). The main associated diagnoses were diabetes mellitus (20.2%), cardiac disease, including arrhythmias (14%) and cardiomyopathy (dilated 3.8%; peri-, endo-, myocarditis 1.3%), liver cirrhosis (8.6%), HCC (1.6%), and acute liver failure (0.81%). Of note, HCC was associated with cirrhosis in 1188 patients (43% of HCC patients) and male sex (87%). Diagnostic biopsies were performed in 6023 (3.6%) of those patients and liver transplant was performed in 881 (0.5%). In-hospital mortality occurred in 3638 (2.16%) patients. In this large database study, we found a rising trend in hospitalization for hemochromatosis, possibly due to the increased recognition of this entity and billing for the condition. The incidence of cirrhosis in hemochromatosis was found to be similar to other studies (8.6% vs 9%). However, the rate of HCC was lower than previous reports (1.6% vs 2.2%–14.9%), and only 43% of HCC was associated with cirrhosis. This raises important pathophysiologic questions regarding the impact of iron overload in HCC. There has been an increase in the rate of hospitalization for patients with a diagnosis of hemochromatosis. This may be related to an increased recognition of hemochromatosis as the underlying etiology for conditions such as diabetes, cardiomyopathy, cirrhosis, and HCC. Further prospective studies are needed to clarify the burden of liver disease in HH and secondary iron overload.
How Digital Systems Are Used in Swedish Home Care Nursing Practice
Authors: Persson Johanna , Larsson Roger , Erlingsdottir Gudbjörg , Rydenfält Christofer
Published: January 2023

This study investigates how digital technology is used (or not used) in home care nursing, to identify challenges and opportunities that can move the digitalization of home care nursing forward. The use of digital technology in daily practices of home care nursing was analyzed based on semistructured interviews in four Swedish home care organizations. The results correspond to the two initial stages of a design thinking process: (1) knowledge about users and the use context, presented as an up-to-date description of how digital technology has affected home care nursing practice, and (2) definition of areas for improvement, presented as challenges and opportunities. We identified the following areas to proceed with in the subsequent stages of designing home care nursing digitalization: (1) nurses' ability to access information and conduct documentation in the field, particularly how new digital systems are integrated with existing routines and systems; (2) the multitude of communication processes that nurses must manage, including communication channels that are used and the level of synchronicity; (3) an increasingly complex digital working environment, where evaluating existing systems and routines is one way to learn where improvements can be most efficient.
Histopathologic features and parameters predicting recurrence potential of small renal masses
Authors: Bajramović Senad , Hasanović Berina , Alić Jasmin , Šabanović Bajramović Nirvana , Aganović Damir
Published: January 2023

Background

Small renal masses (SRMs) are defined as contrast-enhanced masses with a diameter of ≤4 cm, usually consistent with clinical stage T1a renal cell carcinoma (RCC). This study aimed to explore the histopathological features of a contemporary series of SRMs and investigate parameters that could predict their pathological nature, metastatic potential, and recurrence potential.

Materials and methods

Small renal masses were identified in 166 of 427 patients who underwent surgery for suspected RCC. The radical nephrectomy/partial nephrectomy ratio was 1:44, and autotransplantation was performed in a single case. Variables associated with metastatic recurrence of SRM were analyzed using χ2 and logistic regression models.

Results

Renal cell carcinoma was confirmed in 86% (n = 143) of cases, whereas benign tumors were present in 14% (n = 23) of cases. Seventeen percent of the RCC cases were high-grade (Fuhrman G3–4). Among SRMs with a diameter of >2 cm, 71% were malignant. The mean ± standard deviation diameter of the removed SRMs was 28 ± 12 mm, significantly higher in the malignant SRMs group (31 ± 8 vs. 24 ± 9 mm) (p = 0.005). During follow-up, local recurrence was identified in 4 patients versus new distant metastasis in 11 patients. Metastatic lesions were detected in the lungs (1.8%), bone (1.2%), distant (1.9%) and regional lymph nodes (1.2%), liver (0.6%), and multiple organs (2.4%). Patients with malignant SRMs were significantly older than those with benign tumors (p = 0.036). The multivariate analysis identified tumor size, Fuhrman grade, stage, nodal and distant metastasis status, tumor localization, and treatment modality as characteristics significant for tumor recurrence.

Conclusions

The majority of treated neoplasms were malignant, but their incidence was low among SRMs with a diameter of <2 cm. Our results emphasized the importance of histopathological features and treatment modalities in predicting malignant recurrence.
Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Authors: Zhang Liangjun , Pan Qiong , Zhang Lu , Xia Haihan , Liao Junwei , Zhang Xiaoxun , Zhao Nan , Xie Qiaoling , Liao Min , Tan Ya , Li Qiao , Zhu Jinfei , Li Ling , Fan Shijun , Li Jianwei , Zhang Chengcheng , Cai Shi-Ying , Boyer James L. , Chai Jin
Published: January 2023

Background and Aims:

Bile acids trigger a hepatic inflammatory response, causing cholestatic liver injury. Runt-related transcription factor-1 (RUNX1), primarily known as a master modulator in hematopoiesis, plays a pivotal role in mediating inflammatory responses. However, RUNX1 in hepatocytes is poorly characterized, and its role in cholestasis is unclear. Herein, we aimed to investigate the role of hepatic RUNX1 and its underlying mechanisms in cholestasis.

Approach and Results:

Hepatic expression of RUNX1 was examined in cholestatic patients and mouse models. Mice with liver-specific ablation of Runx1 were generated. Bile duct ligation and 1% cholic acid diet were used to induce cholestasis in mice. Primary mouse hepatocytes and the human hepatoma PLC/RPF/5-ASBT cell line were used for mechanistic studies. Hepatic RUNX1 mRNA and protein levels were markedly increased in cholestatic patients and mice. Liver-specific deletion of Runx1 aggravated inflammation and liver injury in cholestatic mice induced by bile duct ligation or 1% cholic acid feeding. Mechanistic studies indicated that elevated bile acids stimulated RUNX1 expression by activating the RUNX1-P2 promoter through JAK/STAT3 signaling. Increased RUNX1 is directly bound to the promotor region of inflammatory chemokines, including CCL2 and CXCL2, and transcriptionally repressed their expression in hepatocytes, leading to attenuation of liver inflammatory response. Blocking the JAK signaling or STAT3 phosphorylation completely abolished RUNX1 repression of bile acid–induced CCL2 and CXCL2 in hepatocytes.

Conclusions:

This study has gained initial evidence establishing the functional role of hepatocyte RUNX1 in alleviating liver inflammation during cholestasis through JAK/STAT3 signaling. Modulating hepatic RUNX1 activity could be a new therapeutic target for cholestasis.
Machine Learning and Health Care
Authors: Atkinson J. Graham , Atkinson Elizabeth G.
Published: January 2023

We discuss the potential for machine learning (ML) and artificial intelligence (AI) to improve health care, while detailing caveats and important considerations to ensure unbiased and equitable implementation. If disparities exist in the data used to train ML algorithms, they must be recognized and accounted for, so they do not bias performance accuracy or are not interpreted by the algorithm as simply a lack of need. We pay particular attention to an area in which bias in data composition is particularly striking, that is in large-scale genetics databases, as people of European descent are vastly overrepresented in the existing resources.
Patient-Centered Payment for Care of Chronic Conditions
Authors: Miller Harold D.
Published: January 2023

Current payment systems make it difficult for both specialists and primary care practices to provide all of the services needed by patients with chronic conditions. “Value-based payment” programs have failed to solve these problems. In a patient-centered payment system, there should be 4 separate payments designed specifically to support each of the phases of chronic condition care: (1) Diagnosis Payment, (2) Care Planning Payment, (3) Initial Condition Management Payment, and (4) Monthly Condition Management Payments. Physicians should be accountable for delivering evidence-based services to patients in each phase of care, and payment amounts should be higher for more complex patients.
Interprofessional Ambulatory Staff Perceptions of Pandemic Preparedness
Authors: Bernhardt Jean M. , Benoit Elizabeth B.
Published: January 2023

The COVID-19 pandemic forced us to face the growing realization that our expectations of staff redeployed to areas other than their usual role did not fully align with their perceptions of safety, competence, and teamwork. This mixed-methods study assessed perceptions of role, preparedness, and management among staff who were deployed from March through June 2020. Our findings support that the rapid reassignment of interprofessional role groups to respiratory illness clinics in the first wave, albeit necessary at the time, may not be the best response in future infectious disease outbreaks.
Quantifying the Risk for Hospital Readmission When Physical Therapist Discharge Recommendations Are Not Followed
Authors: Wright Jonathan R. , Koch-Hanes Trisha , Cortney Ciera , Lutjens Kathryn , Raines Kristopher , Young Daniel
Published: January 2023

Purpose:

Studies suggest that implementing physical therapist discharge recommendations decreases 30-day hospital readmissions but may have miscounted readmissions. The purpose of this study was to obtain accurate readmission data and calculate the risk for readmission when therapists' recommendations are not followed.

Methods:

We conducted this prospective cohort study at a hospital in the Northwestern United States. Two hundred sixty-nine hospitalized participants with physical therapy orders consented to medical record data extraction and participated in a follow-up phone call. We compared physical therapist discharge recommendations to the actual discharge setting and services established for participants as documented in their medical record. Thirty days after discharge, we called participants to ask whether they had been readmitted to any hospital. We then analyzed associations between readmissions and the mismatch of therapist recommendations and participants' actual discharge locations and services received.

Results:

Twenty-one percent of discharges did not match the location and/or services recommended by the physical therapist. Sixty-six of the 269 participants were readmitted within 30 days. The odds for readmission were 2.3 times greater among participants who did not discharge to the location with the services recommended by their physical therapist.

Conclusions:

When physical therapist discharge location and services recommendations are not implemented, patients have increased risk of hospital readmission. This finding should inform stakeholders involved in discharge planning on the effect of following recommendations.
Halo Nevi in the Pediatric Population
Authors: So Jodi Y. , Admani Shehla
Published: January 2023

Halo nevi are commonly observed in children and adolescents and may coexist with other disorders including vitiligo and Turner syndrome. This review discusses the epidemiology, pathophysiology, diagnosis, and management of halo nevi, with a particular emphasis on pediatric patients.