bluuebunny/crossref_metadata_2025 huggingface dataset:
Marketing
Authors: Combe Colin
Published: September 2023

This chapter focuses on key elements of managing the marketing function in organisations. It begins with a definition of marketing. Then, it presents the different types of marketing strategies available to managers. It outlines the development of the marketing plan, a key component of the marketing process. The chapter considers models of marketing to analyse the challenges and opportunities that present themselves through the identification and exploitation of different market segments. It shows the links into the marketing mix using the four P’s model: product, place, price, and promotion. New approaches to marketing are highlighted and discussed. The use of new media applications as a means of spreading the marketing message to consumers and other stakeholders is analysed. Finally, the chapter concludes by discussing the advantages and problems associated with the application of customer relationship management systems for marketing purposes.
Introduction to marketing research
Authors: Bradley Nigel
Published: September 2023

This chapter examines marketing research in general and distinguishes between the terms market and marketing research. It explains ‘insight management’. It describes how this industry operates across the world, who commissions research and how much money is spent. International suppliers and trade bodies are introduced, along with the types of research and services available. The chapter provides a description of jobs that exist in the marketing research sector that could assist in planning a career.
Career management: creating opportunities
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter focuses on creating opportunities. First, it notes the considered alternative routes for seeking graduate employment in an effort to enhance employability. It lists possible alternatives such as applying for jobs on spec, networking, temporary work, and offering free services on trial. The chapter explains the possibility of entrepreneurship and freelance work. Moreover, it explains the three main entrepreneurial competencies: cognition, social and action-oriented. The chapter also includes ways of finding freelance work. It delivers helpful advice on how to manage businesses such as marketing, price, promotion, and the customer relationship. The chapter highlights the importance of optimism and having a mentor. It explicates visualizing success as well.
A telomere-to-telomere reference genome provides genetic insight into the pentacyclic triterpenoid biosynthesis inChaenomeles speciosa
Authors: He Shaofang , Weng Duanyang , Zhang Yipeng , Kong Qiusheng , Wang Keyue , Jing Naliang , Li Fengfeng , Ge Yuebin , Xiong Hui , Wu Lei , Xie De-Yu , Feng Shengqiu , Yu Xiaqing , Wang Xuekui , Shu Shaohua , Mei Zhinan
Published: September 2023

Chaenomeles speciosa (2n = 34), a medicinal and edible plant in the Rosaceae, is commonly used in traditional Chinese medicine. To date, the lack of genomic sequence and genetic studies has impeded efforts to improve its medicinal value. Herein, we report the use of an integrative approach involving PacBio HiFi (third-generation) sequencing and Hi-C scaffolding to assemble a high-quality telomere-to-telomere genome of C. speciosa. The genome comprised 650.4 Mb with a contig N50 of 35.5 Mb. Of these, 632.3 Mb were anchored to 17 pseudo-chromosomes, in which 12, 4, and 1 pseudo-chromosomes were represented by a single contig, two contigs, and four contigs, respectively. Eleven pseudo-chromosomes had telomere repeats at both ends, and four had telomere repeats at a single end. Repetitive sequences accounted for 49.5% of the genome, while a total of 45 515 protein-coding genes have been annotated. The genome size of C. speciosa was relatively similar to that of Malus domestica. Expanded or contracted gene families were identified and investigated for their association with different plant metabolisms or biological processes. In particular, functional annotation characterized gene families that were associated with the biosynthetic pathway of oleanolic and ursolic acids, two abundant pentacyclic triterpenoids in the fruits of C. speciosa. Taken together, this telomere-to-telomere and chromosome-level genome of C. speciosa not only provides a valuable resource to enhance understanding of the biosynthesis of medicinal compounds in tissues, but also promotes understanding of the evolution of the Rosaceae.
The boundary between digital goods and E-services in cross-border E-commerce and implication for non-discrimination under the WTO system
Authors: Tanodomdej Papawadee
Published: September 2023

One of the biggest challenges of implementing value-added tax (VAT) collection on cross-border digital goods and services is the compliance with World Trade Organization (WTO) obligations. The lack of a clear distinction between goods and services in the WTO agreements and divergent classifications adopted by states have led to fragmented and inconsistent VAT collection, potentially creating trade barriers in international e-commerce. This article analyses various approaches to classify goods and services including technological neutrality and tradability. It also uses the modernization of Thailand’s VAT system as a case study to demonstrate the complexity of categorizing digital goods and services for VAT enforcement in international e-commerce. It finds that technological neutrality and tradability are key criteria to separate digital goods from e-services for the proper implementation of WTO obligations. The article concludes with remarks on the correlation between categorizing digital goods and services in VAT collection and protectionism in cross-border e-commerce.
Thin Polytopes: Lattice Polytopes With Vanishing Local h*-Polynomial
Authors: Borger Christopher , Kretschmer Andreas , Nill Benjamin
Published: September 2023

In this paper, we study the novel notion of thin polytopes: lattice polytopes whose local $h^{*}$-polynomials vanish. The local $h^{*}$-polynomial is an important invariant in modern Ehrhart theory. Its definition goes back to Stanley with fundamental results achieved by Karu, Borisov, and Mavlyutov; Schepers; and Katz and Stapledon. The study of thin simplices was originally proposed by Gelfand, Kapranov, and Zelevinsky, where in this case the local $h^{*}$-polynomial simply equals its so-called box polynomial. Our main results are the complete classification of thin polytopes up to dimension 3 and the characterization of thinness for Gorenstein polytopes. The paper also includes an introduction to the local $h^{*}$-polynomial with a survey of previous results.
Phloem anatomy restricts root system architecture development: theoretical clues from in silico experiments
Authors: Zhou Xiao-Ran , Schnepf Andrea , Vanderborght Jan , Leitner Daniel , Vereecken Harry , Lobet Guillaume
Published: September 2023

Plant growth and development involve the integration of numerous processes, influenced by both endogenous and exogenous factors. At any given time during a plant’s life cycle, the plant architecture is a readout of this continuous integration. However, untangling the individual factors and processes involved in the plant development and quantifying their influence on the plant developmental process is experimentally challenging. Here we used a combination of computational plant models (CPlantBox and PiafMunch) to help understand experimental findings about how local phloem anatomical features influence the root system architecture. Our hypothesis was that strong local phloem resistance would restrict local carbon flow and locally modify root growth patterns. To test this hypothesis, we simulated the mutual interplay between the root system architecture development and the carbohydrate distribution to provide a plausible mechanistic explanation for several experimental results. Our in silico experiments highlighted the strong influence of local phloem hydraulics on the root growth rates, growth duration and final length. The model result showed that a higher phloem resistivity leads to shorter roots due to the reduced flow of carbon within the root system. This effect was due to local properties of individual roots, and not linked to any of the pleiotropic effects at the root system level. Our results open a door to a better representation of growth processes in a plant computational model.
Artificial neural network approaches to identify maternal and infant risk and asset factors using Peridata.Net: a WI-MIOS study
Authors: Holt Jeana M , Talsma AkkeNeel , Johnson Teresa S , Ehlinger Timothy
Published: September 2023

Objective

To analyze PeriData.Net, a clinical registry with linked maternal–infant hospital data of Milwaukee County residents, to demonstrate a predictive analytic approach to perinatal infant risk assessment.

Materials and Methods

Using unsupervised learning, we identified infant birth clusters with similar multivariate health indicator patterns, measured using perinatal variables from 2008 to 2019 from n = 43 969 clinical registry records in Milwaukee County, WI, followed by supervised learning risk-propagation modeling to identify key maternal factors. To understand the relationship between socioeconomic status (SES) and birth outcome cluster assignment, we recoded zip codes in Peridata.Net according to SES level.

Results

Three self-organizing map clusters describe infant birth outcome patterns that are similar in the multivariate space. Birth outcome clusters showed higher hazard birth outcome patterns in cluster 3 than clusters 1 and 2. Cluster 3 was associated with lower Apgar scores at 1 and 5 min after birth, shorter infant length, and premature birth. Prediction profiles of birth clusters indicate the most sensitivity to pregnancy weight loss and prenatal visits. Majority of infants assigned to cluster 3 were in the 2 lowest SES levels.

Discussion

Using an extensive perinatal clinical registry, we found that the strongest predictive performance, when considering cluster membership using supervised learning, was achieved by incorporating social and behavioral risk factors. There were inequalities in infant birth outcomes based on SES.

Conclusion

Identifying infant risk hazard profiles can contribute to knowledge discovery and guide future research directions. Additionally, presenting the results to community members can build consensus for community-identified health and risk indicator prioritization for intervention development.
Pork quality traits and associated muscle metabolic changes in pigs under chronic prenatal and postnatal heat stress
Authors: Lebret Bénédicte , Serviento Aira Maye , Renaudeau David
Published: September 2023

Chronic heat stress (HS) is a major concern affecting pig growth performance and metabolism, with potential consequences on carcass and meat quality traits. The objective of this study was to assess the influence of prenatal (PE) and growing (GE) thermal environments, and their combination, on muscle metabolism, carcass characteristics, and pork quality. From 6 to 109 d of gestation, 12 sows (1 per block) were kept under thermoneutral (TN) conditions (cyclic 18 to 24 °C; PTN) and 12 sows under chronic HS (cyclic 28 to 34 °C; PHS). Two female offspring per sow were selected based on body weight at weaning, for a total of 48 female pigs (12 blocks of 2 sisters from each PE), and one sister was placed in each GE. Gilts were housed from 82 to 140 d of age under cyclic GTN (18 to 24 °C; n = 24) or GHS (28 to 34 °C; n = 24) environments. Data were analyzed using a mixed model including PE, GE, and PE × GE interaction as main effects, and sire, sow within PE, pen within PE × GE, and slaughter day (for plasma, muscle, and meat traits) as random effects. No significant PE × GE interaction was found on any trait under study (P ≥ 0.05). Prenatal HS did not affect growth performance and carcass traits (P ≥ 0.05). Compared with GTN, GHS pigs had lower average daily feed intake, average daily gain, and hot carcass weight (P < 0.01), but similar carcass lean meat content (P ≥ 0.05). Prenatal HS had scarce effects on pork quality, with only higher a* and C* values (P < 0.05) in the Gluteus superficialis. Growing HS led to a higher pH 24 h (P < 0.05) in the Longissimus thoracis et lumborum (LTL) and ham muscles, and higher meat quality index in the ham muscles. In contrast, quality traits of the Semispinalis capitis (SC) were not affected by either PE or GE (P > 0.05). Except a tendency for a higher citrate synthase activity in the SC (P = 0.065), PHS did not affect muscle metabolism. Growing HS induced muscle-specific metabolic responses, with reduced glycolytic potential (P < 0.01) and metabolic enzyme activities (P < 0.05) in the glycolytic LTL, but not in the oxidative SC (P > 0.05). Plasma glucose content at slaughter was lower in the GHS compared with GTN pigs (P = 0.002), indicating an altered energy metabolism in pigs under GHS. Altogether, growing HS altered growth without affecting carcass traits, but improved technological quality of loin and ham. Prenatal HS, alone or combined with GHS, had limited or even no effect on carcass and pork quality.
Accuracy analysis for machine tool spindles considering full parallel connections and form errors based on skin model shapes
Authors: Hu Xiaokun , Zhao Qiangqiang , Yang Yitao , Wan Shaoke , Sun Yanhui , Hong Jun
Published: September 2023

The rotation accuracy of a machine tool spindle is essential for ensuring the machining precision. Due to the existence of manufacturing and assembly errors, the rotation accuracy of the spindle will be inevitably impacted and degraded. Therefore, to reduce the influence of the errors and improve the work performance, this paper focuses on accuracy analysis for the spindle and a novel optimization-oriented skin model shape method to tackle this highly complex problem. First, a structural analysis of the spindle is carried out to elaborate the intractable full parallel collections in the assembly. Then, based on the iterative closest point method, the deviation propagation of the spindle considering complex full parallel collections is transformed into an optimization problem, in which the skin model shapes and small displacement torsor are utilized to represent the form and pose errors of the part, respectively. By solving the optimization problem, assembly accuracy analysis for the spindle in terms of full parallel connections and form errors is accordingly achieved. On this basis, the tolerance analysis model of the spindle is also comprehensively established by employing the corresponding error simulation. Finally, measurement experiments are conducted to validate the effectiveness of the proposed method. The experiments show the predicted rotation runout and tolerance magnitude are close to the testing results, therefore indicating the proposed method can provide effective accuracy analysis for spindles.
Socioeconomic status and inequities in treatment initiation and survival among patients with cancer, 2011-2022
Authors: Guadamuz Jenny S , Wang Xiaoliang , Ryals Cleo A , Miksad Rebecca A , Snider Jeremy , Walters James , Calip Gregory S
Published: September 2023

Background

Lower neighborhood socioeconomic status (SES) is associated with suboptimal cancer care and reduced survival. Most studies examining cancer inequities across area-level socioeconomic status tend to use less granular or unidimensional measures and pre-date the COVID-19 pandemic. Here, we examined the association of area-level socioeconomic status on real-world treatment initiation and overall survival among adults with 20 common cancers.

Methods

This retrospective cohort study used electronic health record–derived deidentified data (Flatiron Health Research Database, 2011-2022) linked to US Census Bureau data from the American Community Survey (2015-2019). Area-level socioeconomic status quintiles (based on a measure incorporating income, home values, rental costs, poverty, blue-collar employment, unemployment, and education information) were computed from the US population and applied to patients based on their mailing address. Associations were examined using Cox proportional hazards models adjusted for diagnosis year, age, sex, performance status, stage, and cancer type.

Results

This cohort included 291 419 patients (47.7% female; median age = 68 years). Patients from low–SES areas were younger and more likely to be Black (21.9% vs 3.3%) or Latinx (8.4% vs 3.0%) than those in high–SES areas. Living in low–SES areas (vs high) was associated with lower treatment rates (hazard ratio = 0.94 [95% confidence interval = 0.93 to 0.95]) and reduced survival (median real-world overall survival = 21.4 vs 29.5 months, hazard ratio = 1.20 [95% confidence interval = 1.18 to 1.22]). Treatment and survival inequities were observed in 9 and 19 cancer types, respectively. Area-level socioeconomic inequities in treatment and survival remained statistically significant in the COVID-19 era (after March 2020).

Conclusion

To reduce inequities in cancer outcomes, efforts that target marginalized, low–socioeconomic status neighborhoods are necessary.
Medicaid expansion is associated with treatment receipt, timeliness, and outcomes among young adults with breast cancer
Authors: Ji Xu , Shi Kewei Sylvia , Ruddy Kathryn J , Zhao Jingxuan , Mertens Ann C , Yabroff K Robin , Castellino Sharon M , Han Xuesong
Published: September 2023

Female breast cancer is a common cancer in young adults, an age group with the highest uninsured rate. Among 51 675 young adult women (ages 18-39 years) diagnosed with breast cancer between 2011 and 2018 in the National Cancer Database, we estimated changes in guideline-concordant treatment receipt, treatment timeliness, and survival associated with the Affordable Care Act Medicaid expansion. Of young adults with stage I-III estrogen receptor–positive or progesterone receptor–positive breast cancer, Medicaid expansion was associated with a net increase of 2.42 percentage points (95% confidence interval [CI] = 0.56 to 4.28 percentage points) in the percentage receiving endocrine therapy. Among all young adults with stage I-III breast cancer, Medicaid expansion was associated with a net reduction of 1.65 percentage points (95% CI = 0.08 to 3.22 percentage points) in treatment delays defined as treatment initiation of at least 60 days after diagnosis and a net increase of 1.00 percentage points (95% CI = 0.21 to 1.79 percentage points) in 2-year overall survival. Our study provides evidence of benefit in cancer care and outcomes from Medicaid expansion among the young adult population.
Advancing the science of integrating multiple interventions by blending and bundling
Authors: Villalobos Aubrey , Chambers David A
Published: September 2023

Cancer prevention and control research has produced a variety of effective interventions over the years, though most are single disease focused. To meet the Cancer Moonshot goal to reduce the cancer death rate by 50% by 2047, it may be necessary to overcome the limitations of siloed interventions that do not meet people’s multiple needs and limitations in system capacity to deliver the increasing number of interventions in parallel. In this article, we propose integrating multiple evidence-based interventions as a potential solution. We define 2 types of integrated interventions, blended and bundled, and provide examples to illustrate each. We then offer a schematic and outline considerations for how to assemble blended or bundled interventions including looking at the intervention need or opportunity along the cancer continuum as well as co-occurring behaviors or motivations. We also discuss delivery workflow integration considerations including social-ecological level(s), context or setting, implementer, and intended beneficiary. Finally, in assembling integrated interventions, we encourage consideration of practice-based expertise and community and/or patient input. After assembly, we share thoughts related to implementation and evaluation of blended or bundled interventions. To conclude the article, we present multiple research opportunities in this space. With swift progress on these research directions, cancer prevention and control interventionists and implementation scientists can contribute to achieving the promise of the reignited Cancer Moonshot.
Evusheld, a SARS-CoV-2 spike protein–directed attachment inhibitor, appears in serum protein electrophoresis and immunofixation: a case study
Authors: Shah Sumit K , Hagrass Hoda A
Published: September 2023

Serum protein electrophoresis (SPE) and immunofixation (IFE) assays are commonly used to diagnose and monitor patients with multiple myeloma (MM).

Identifying analytical interferences in SPE and IFE caused by therapeutic monoclonal antibodies (tmAbs) can be challenging. Here we report the case of a 72-year-old male with a long history of relapsed immunoglobulin (Ig)G kappa MM. A follow-up SPE showed the original peak plus 2 additional cathode peaks. Immunofixation was ordered as a reflex test to investigate the new peaks that showed initial patient monoclonal IgG kappa in addition to 2 restricted bands of the IgG kappa type. Therapeutic monoclonal antibody interference was suspected and the patient’s chart was reviewed. The patient was not on any antimyeloma monoclonal antibody therapy. However, preexposure prophylaxis therapeutic monoclonal antibodies tixagevimab plus cilgavimab (Evusheld) for severe acute SARS-CoV-2 was administered approximately 45 minutes before sample collection, which led to the identifiable spikes and correlated bands. After 2 days, the IgG kappa bands disappeared, confirming this therapy’s effect on SPE and IFE. Therefore, clinical pathologists should be aware of when providers prescribe new monoclonal antibody therapy and become familiar with the position of commonly prescribed (tmAbs) therapies at their institutions.
Predictors of mortality and transfusion requirements in venoarterial extracorporeal membrane oxygenation patients
Authors: Kim Jongmin , Yeo Hye Ju , Cho Woo Hyun , Lee Hyun-Ji
Published: September 2023

Objective

The aim of this study was to evaluate the prognostic impact of variables, including thrombocytopenia and the amount of platelet transfusion, for predicting survival in venoarterial extracorporeal membrane oxygenation (ECMO) recipients. Additionally, we aimed to identify the predictors of increased transfusion requirement during venoarterial ECMO support.

Methods

All patients who received venoarterial ECMO between December 2008 and March 2020 were retrospectively analyzed. Univariate and multivariate Cox regressions were used to evaluate in-hospital mortality according to variables including thrombocytopenia and daily average of platelet concentrate transfusion. Stepwise multiple linear regression analysis was used to identify independent predictors for transfusion requirements.

Results

Analysis of 218 patients demonstrated severe thrombocytopenia as an independent predictor of in-hospital mortality (hazard ratio = 2.840, 95% CI: 1.593-5.063, P < .001), along with age, pre-ECMO cardiac arrest, and pH. In contrast, the amount of platelet transfusion was not associated with in-hospital mortality. Multiple variables, including the type of indication for ECMO were associated with transfusion requirements.

Conclusion

Our findings identified severe thrombocytopenia as an independent prognostic factor of in-hospital mortality. However, daily average platelet transfusion was not associated with survival outcomes. Additionally, our study identified predictive variables of increased transfusion requirements.
Probabilistic classification of infrared-selected targets for SPHEREx mission: in search of young stellar objects
Authors: Lakshmipathaiah K , Vig S , Ashby Matthew L N , Hora Joseph L , Kang Miju , Gorthi Rama Krishna Sai S
Published: September 2023

We apply machine learning algorithms to classify infrared (IR)-selected targets for NASA’s upcoming Spectro-Photometer for the History of the Universe, Epoch of Reionization and Ices Explorer (SPHEREx) mission. In particular, we are interested in classifying young stellar objects (YSOs), which are essential for understanding the star formation process. Our approach differs from previous works, which have relied heavily on broad-band colour criteria to classify IR-bright objects, and are typically implemented in colour–colour and colour–magnitude diagrams. However, these methods do not state the confidence associated with the classification and the results from these methods are quite ambiguous due to the overlap of different source types in these diagrams. Here, we utilize photometric colours and magnitudes from seven near- and mid-IR bands simultaneously and employ machine and deep learning algorithms to carry out probabilistic classification of YSOs, asymptotic giant branch (AGB) stars, active galactic nuclei (AGNs), and main-sequence (MS) stars. Our approach also subclassifies YSOs into Class I, II, III, and flat spectrum YSOs, and AGB stars into carbon-rich and oxygen-rich AGB stars. We apply our methods to IR-selected targets compiled in preparation for SPHEREx which are likely to include YSOs and other classes of objects. Our classification indicates that out of 8308 384 sources, 1966 340 have class prediction with probability exceeding 90 per cent, amongst which $\sim 1.7~{{\ \rm per\ cent}}$ are YSOs, $\sim 58.2~{{\ \rm per\ cent}}$ are AGB stars, $\sim 40~{{\ \rm per\ cent}}$ are (reddened) MS stars, and $\sim 0.1~{{\ \rm per\ cent}}$ are AGNs whose red broad-band colours mimic YSOs. We validate our classification using the spatial distributions of predicted YSOs towards the Cygnus-X star-forming complex, as well as AGB stars across the Galactic plane.
The long-term safety and tolerability of anifrolumab for patients with systemic lupus erythematosus in Japan: TULIP-LTE subgroup analysis
Authors: Tanaka Yoshiya , Atsumi Tatsuya , Okada Masato , Miyamura Tomoya , Ishii Tomonori , Nishiyama Susumu , Matsumura Ryutaro , Kawakami Atsushi , Hayashi Nobuya , Abreu Gabriel , Yavuz Sule , Lindholm Catharina , Al-Mossawi Hussein , Takeuchi Tsutomu
Published: September 2023

Objectives

Evaluate the long-term safety and tolerability of anifrolumab 300 mg, alongside standard therapy, in patients from Japan with systemic lupus erythematosus (SLE) in the TULIP-LTE trial (NCT02794285).

Methods

TULIP-LTE was a 3-year, randomized, double-blind, placebo-controlled long-term extension (LTE) of the TULIP trials. The primary safety outcome included serious adverse events (SAEs) and AEs of special interest (AESIs) during the LTE period. Exploratory efficacy outcomes included SLE Disease Activity Index 2000 (SLEDAI-2 K) scores and glucocorticoid use. We performed a post hoc subgroup analysis of patients who enrolled in Japan.

Results

Exposure-adjusted incidence rates of SAEs during the LTE and follow-up for patients receiving anifrolumab 300 mg (n = 21) were 8.7 per 100 patient-years; AESIs included influenza (6.9) and herpes zoster (3.5). One of three patients receiving placebo had an SAE (13.9). One patient per group discontinued due to an AE. There were no deaths. During the TULIP + LTE period, patients receiving anifrolumab 300 mg (n = 24) had sustained reduction from baseline in mean SLEDAI-2 K scores and cumulative glucocorticoid dosage.

Conclusions

Anifrolumab 300 mg showed a favourable benefit-risk profile for the long-term treatment of adult patients with moderate to severe SLE from Japan, with safety, tolerability, and efficacy profiles consistent with the overall population.
Early kinetics of donor-derived cell-free DNA after transplantation predicts renal graft recovery and long-term function
Authors: Cucchiari David , Cuadrado-Payan Elena , Gonzalez-Roca Eva , Revuelta Ignacio , Argudo Maria , Ramirez-Bajo Maria José , Ventura-Aguiar Pedro , Rovira Jordi , Bañon-Maneus Elisenda , Montagud-Marrahi Enrique , Rodriguez-Espinosa Diana , Cacho Judit , Arana Carolt , Torregrosa Vicens , Esforzado Nuria , Cofàn Frederic , Oppenheimer Frederic , Musquera Mireia , Peri Lluís , Casas Silvia , Dholakia Sham , Palou Eduard , Campistol Josep M , Bayés Beatriu , Puig Joan Anton , Diekmann Fritz
Published: September 2023

Background

Ischemia–reperfusion injury (IRI) upon transplantation is one of the most impactful events that the kidney graft suffers during its life. Its clinical manifestation in the recipient, delayed graft function (DGF), has serious prognostic consequences. However, the different definitions of DGF are subject to physicians’ choices and centers’ policies, and a more objective tool to quantify IRI is needed. Here, we propose the use of donor-derived cell-free DNA (ddcfDNA) for this scope.

Methods

ddcfDNA was assessed in 61 kidney transplant recipients of either living or deceased donors at 24 h, and 7, 14 and 30 days after transplantation using the AlloSeq cfDNA Kit (CareDx, San Francisco, CA, USA). Patients were followed-up for 6 months and 7-year graft survival was estimated through the complete and functional iBox tool.

Results

Twenty-four-hour ddcfDNA was associated with functional DGF [7.20% (2.35%–15.50%) in patients with functional DGF versus 2.70% (1.55%–4.05%) in patients without it, P = .023] and 6-month estimated glomerular filtration rate (r = –0.311, P = .023). At Day 7 after transplantation, ddcfDNA was associated with dialysis duration in DGF patients (r = 0.612, P = .005) and worse 7-year iBox-estimated graft survival probability (β –0.42, P = .001) at multivariable analysis. Patients with early normalization of ddcfDNA (<0.5% at 1 week) had improved functional iBox-estimated probability of graft survival (79.5 ± 16.8%) in comparison with patients with 7-day ddcfDNA ≥0.5% (67.7 ± 24.1%) (P = .047).

Conclusions

ddcfDNA early kinetics after transplantation reflect recovery from IRI and are associated with short-, medium- and long-term graft outcome. This may provide a more objective estimate of IRI severity in comparison with the clinical-based definitions of DGF.
The effect of airtime incentives to improve participation in noncommunicable disease interactive voice response surveys: randomized controlled trials in Colombia and Tanzania
Authors: Maniar Vidhi D , Gibson Dustin G , Labrique Alain B , Ali Joseph , Vecino-Ortiz Andres I , Torres-Quintero Angelica , Puerto-García Stephanie , Solorzano-Barrera Camila , Masanja Honorati , Kagoro Frank , Pariyo George W
Published: September 2023

Objective: We assessed whether airtime incentives can improve cooperation and response rates for a noncommunicable disease interactive voice response survey in Colombia and Tanzania.

Methods: Participants were randomized to four arms: (a) no incentive; (b) 1X incentive, where X equals to 5000 Colombian Pesos (US$1.35) or 3000 Tanzanian shillings (TSh; US$1.29); (3) 2X incentive; or (4) lottery incentive of 50 000 COP (US$18.90) or 50 000 TSh (US$21.50), where the odds of winning the lottery were 1:20. Adults aged 18 years and older who possessed a functioning mobile phone were sampled using random digit dialling. We analyzed the primary outcomes, cooperation and response rates using a log binomial regression model as computed by the American Association of Public Opinion Research. Results: In Colombia, between October 15 to November 13, 2018, 125 745 phone calls were made. In Tanzania, 67 800 random digit dial phone calls were made from August 9 to 28, 2018. In Colombia, we observed significantly higher cooperation rates in the 1X, 2X and lottery incentive groups compared to control. Additionally, response rates were significantly higher in the 1X and 2X incentive groups but were significantly lower in lottery group compared to control. In Tanzania, both cooperation and response rates were significantly higher in the 1X, 2X and lottery incentive groups compared to control. Conclusion: Except for the lottery incentive arm in Colombia, which yielded a response rate lower than the control, the introduction of airtime incentives significantly improved cooperation and response rates in Colombia and Tanzania, with no notable variations between the incentive arms.
A Small-Molecule Modulator Affecting the Clock-Associated PSEUDO-RESPONSE REGULATOR 7 Amount
Authors: Uehara Takahiro N , Takao Saori , Matsuo Hiromi , Saito Ami N , Ota Eisuke , Ono Azusa , Itami Kenichiro , Kinoshita Toshinori , Yamashino Takafumi , Yamaguchi Junichiro , Nakamichi Norihito
Published: September 2023

Circadian clocks are biological timekeeping systems that coordinate genetic, metabolic and physiological behaviors with the external day–night cycle. The clock in plants relies on the transcriptional-translational feedback loops transcription-translation feedback loop (TTFL), consisting of transcription factors including PSUEDO-RESPONSE REGULATOR (PRR) proteins, plant lineage–specific transcriptional repressors. Here, we report that a novel synthetic small-molecule modulator, 5-(3,4-dichlorophenyl)-1-phenyl-1,7-dihydro-4H-pyrazolo[3,4-d] pyrimidine-4,6(5H)-dione (TU-892), affects the PRR7 protein amount. A clock reporter line of Arabidopsis was screened against the 10,000 small molecules in the Maybridge Hitfinder 10K chemical library. This screening identified TU-892 as a period-lengthening molecule. Gene expression analyses showed that TU-892 treatment upregulates CIRCADIAN CLOCK–ASSOCIATED 1 (CCA1) mRNA expression. TU-892 treatment reduced the amount of PRR7 protein, a transcriptional repressor of CCA1. Other PRR proteins including TIMING OF CAB EXPRESSION 1 were altered less by TU-892 treatment. TU-892-dependent CCA1 upregulation was attenuated in mutants impaired in PRR7. Collectively, TU-892 is a novel type of clock modulator that reduces the levels of PRR7 protein.
CstPIF4 Integrates Temperature and Circadian Signals and Interacts with CstMYB16 to Repress Anthocyanins in Crocus
Authors: Hussain Khadim , Bhat Zahid Yaqoob , Yadav Arvind Kumar , Singh Deepika , Ashraf Nasheeman
Published: September 2023

Crocus sativus has emerged as an important crop because it is the only commercial source of saffron that contains unique apocarotenoids. Saffron is composed of dried stigmas of Crocus flower and constitutes the most priced spice of the world. Crocus floral organs are dominated by different classes of metabolites. While stigmas are characterized by the presence of apocarotenoids, tepals are rich in flavonoids and anthocyanins. Therefore, an intricate regulatory network might play a role in allowing different compounds to dominate in different organs. Work so far done on Crocus is focussed on apocarotenoid metabolism and its regulation. There are no reports describing the regulation of flavonoids and anthocyanins in Crocus tepals. In this context, we identified an R2R3 transcription factor, CstMYB16, which resembles subgroup 4 (SG4) repressors of Arabidopsis. CstMYB16 is nuclear localized and acts as a repressor. Overexpression of CstMYB16 in Crocus downregulated anthocyanin biosynthesis. The C2/EAR motif was responsible for the repressor activity of CstMYB16. CstMYB16 binds to the promoter of the anthocyanin biosynthetic pathway gene (LDOX) and reduces its expression. CstMYB16 also physically interacts with CstPIF4, which in turn is regulated by temperature and circadian clock. Thus, CstPIF4 integrates these signals and forms a repressor complex with CstMYB16, which is involved in the negative regulation of anthocyanin biosynthesis in Crocus. Independent of CstPIF4, CstMYB16 also represses CstPAP1 expression, which is a component of the MYB-bHLH-WD40 (MBW) complex and positively controls anthocyanin biosynthesis. This is the first report on identifying and describing regulators of anthocyanin biosynthesis in Crocus.
Care and Monitoring of Pregnant Patients With Left Ventricular Assist Devices
Authors: Pacheco Luis D. , Saad Antonio F. , Lick Scott D. , Iturrizaga Jose C. , Saade George R.
Published: September 2023

Cardiovascular disease is one of the leading causes of maternal mortality in the United States. Although still rare, pregnancy in patients with left ventricular assist devices (LVADs) is becoming more common. Typical indications for the use of LVADs in reproductive-aged females include ischemic cardiomyopathy, nonischemic (familial) dilated cardiomyopathy, peripartum cardiomyopathy, and some forms of myocarditis. An LVAD drains blood through a cannula placed into the apex of the left ventricle and then returns it to the proximal aorta bypassing the aortic valve allowing hemodynamic support in parallel with the native circulation. The physiologic changes associated with pregnancy, mainly increased blood volume and hypercoagulability, may adversely affect patients with LVADs, leading to many experts recommending against pregnancy. Maternal-fetal medicine specialists should have a central role within a multidisciplinary team required to provide optimal care for this high-risk group of patients.
Utility of Weekly Laboratory Monitoring in the Expectant Management of Hypertensive Disorders of Pregnancy
Authors: Morgan John A. , Biggio Joseph R. , Martin Jane K. , Mussarat Naiha , McCloskey Shannon , Williams Frank B.
Published: September 2023

Our retrospective cohort study evaluates the diagnostic yield of weekly laboratory surveillance in outpatient management of hypertensive disorders of pregnancy (HDP) based on patient clinical status at the time of laboratory testing. The study included 459 patients and 1,082 laboratory episodes: 356 (32.9%) episodes were performed in the setting of concerning clinical findings and 726 (67.1%) when the patient was asymptomatic. Overall, the diagnostic yield for abnormal laboratory values (n=11) was 1.0% (95% CI 0.4-1.6%) of all assessments performed and 2.4% (95% CI 1.0–3.8%) among all patients in the cohort. The prevalence of abnormal test results was higher in patients with clinical findings (2.8%, 95% CI 1.1–4.5%) compared with those who were asymptomatic (0.1%, 95% CI 0–0.2%) (P<.01). Clinical findings suggestive of worsening disease had a 91% sensitivity (95% CI 59–100%) and a 99% (95% CI 99–100%) negative predictive value for abnormal laboratory values. Directed screening based on signs and symptoms, rather than universal weekly screening, may be a potential strategy to lower costs and reduce multiple blood draws for patients with HDP, because there is a low diagnostic yield for this practice.
The Ins and Outs of IV Fluids in Hemodynamic Resuscitation
Authors: Kaufman David A. , Lopes Marcela , Maviya Niharika , Magder Sheldon A.
Published: September 2023

OBJECTIVES:

Concise definitive review of the physiology of IV fluid (IVF) use in critically ill patients.

DATA SOURCES:

Available literature on PubMed and MEDLINE databases.

STUDY SELECTION:

Basic physiology studies, observational studies, clinical trials, and reviews addressing the physiology of IVF and their use in the critically ill were included.

DATA EXTRACTION:

None.

DATA SYNTHESIS:

We combine clinical and physiologic studies to form a framework for understanding rational and science-based use of fluids and electrolytes.

CONCLUSIONS:

IVF administration is among the most common interventions for critically ill patients. IVF can be classified as crystalloids or colloids, and most crystalloids are sodium salts. They are frequently used to improve hemodynamics during shock states. Many recent clinical trials have sought to understand which kind of IVF might lead to better patient outcomes, especially in sepsis. Rational use of IVF rests on understanding the physiology of the shock state and what to expect IVF will act in those settings. Many questions remain unanswered, and future research should include a physiologic understanding of IVF in study design.
Cervical Chondrocutaneous Branchial Remnant: A Case Report and Review of the Literature
Authors: Saliba Elie , Brem Candice
Published: September 2023

Cervical chondrocutaneous branchial remnant is a rare congenital developmental anomaly typically located on the lateral neck. Histologically, it has the appearance of an accessory tragus demonstrating a central cartilaginous core with surrounding fibrosis located in the subcutaneous tissue. The condition has been associated with a variety of congenital anomalies, particularly involving the auditory, cardiovascular, and visual systems. Given that research-based evidence related to cervical chondrocutaneous branchial remnant in dermatology literature is sparse, we present this case to raise more awareness about this entity among dermatopathologists and review the different histopathologic presentations and possible associated anomalies.
Phenytoin Intoxication in a Patient Receiving a Therapeutic Dose for Postoperative Seizure Prophylaxis: A Case Study
Authors: Prasertsup Warisa , Chomchai Summon , Mekavuthikul Pattaraporn , Phuditshinnapatra Jariya
Published: September 2023

Objective:

Phenytoin is commonly prescribed to prevent postoperative seizures. Despite the rarity of the CYP2C9 genetic polymorphism, which may result in poor phenytoin metabolism, in the Thai population, the authors report a case of phenytoin toxicity in a patient with poor metabolism administered with a standard dose of phenytoin.

Case Report:

A 58-year-old Thai woman presented to the outpatient clinic with a 2-day history of nausea, vomiting, and dizziness. She underwent craniotomy for tumor removal 2 weeks after being diagnosed with tuberculum sellae meningioma. After the surgery, she was prescribed 300 mg of phenytoin daily to prevent seizures. During the physical examination, ataxia, horizontal nystagmus, and cerebellar abnormalities were observed, with an initial serum phenytoin concentration of 58.85 mg/L. The brain imaging results were unremarkable. Omeprazole was the only recognized drug interaction; however, it is highly unlikely to account for this condition. Pharmacogenetic investigation of CYP2C9 revealed a homozygous CYP2C9*3/*3 mutation, which is indicative of suboptimal drug metabolism and can reduce phenytoin metabolism by 50%. This patient was administered repeated dosages of activated charcoal over the course of 2 days. Her symptoms eventually subsided, with the phenytoin levels dropping to 29.51 mg/L.

Conclusions:

In the absence of an overdose history or drug–drug interaction, CYP2C9 polymorphism should be suspected in patients with phenytoin toxicity. In such situations, the phenytoin dosage must be decreased and monitored closely.
Use and outcome of TIPS in hospitalized patients in Germany: A Nationwide study (2007–2018)
Authors: Gu Wenyi , Zeleke Yasmin , Hortlik Hannah , Schaaf Louisa , Uschner Frank E. , Schulz Martin , Tischendorf Michael , Peiffer Kai-Henrik , Brol Maximilian Joseph , Kimmann Markus , Vogl Thomas , Köhler Michael , Meyer Carsten , Gerbes Alexander , Rössle Martin , Laleman Wim , Zipprich Alexander , Steib Christian , Praktiknjo Michael , Trebicka Jonel ,   German TIPS Working Group
Published: September 2023

Background:

The number of complications in patients admitted for cirrhosis has increased over time. Portal hypertension is the driver of many complications of cirrhosis. TIPS placement is the most effective treatment of portal hypertension. The aim of this study was to analyze the use and impact of TIPS placement in the last decade in a nationwide study in Germany.

Methods:

We analyzed 14,598 admissions of patients for TIPS insertions in Germany from 2007 to 2018 using the DRG system, 12,877 out of 2,000,765 total admissions of patients with cirrhosis. All diagnoses and procedures were coded according to ICD-10-CM and OPS codes. The data were analyzed, focusing on the number of admissions and in-hospital mortality.

Results:

The number of TIPS placements increased over the last decade. In-hospital mortality of cirrhotic patients with TIPS decreased when it was placed for severe bleeding (15.2% [TIPS] vs. 19.5% [endoscopy treatment]), ascites (8.7% [TIPS] vs. 14.4% [paracentesis]), and hepatorenal syndrome (HRS) (17.1% [TIPS] vs. 43.3% [no-TIPS]). In the case of bleeding, TIPS significantly decreased in-hospital mortality and also in ascites and HRS. During hospitalization, 22.6% admissions of patients with TIPS insertion showed HE. However, in-hospital mortality in patients admitted with HE grades 1 or 2 and TIPS was lower than in patients without TIPS. In the logistic regression, a higher HE grade(3 and 4), infection, and circulatory disease were found to be independently associated with in-hospital mortality in patients with TIPS insertion.

Conclusion:

Our nationwide study demonstrates that TIPS insertion is increasingly used in Germany. TIPS improves outcomes, especially in patients with ascites and HRS, regardless of lower HE grades, while higher HE grades, infection, and circulatory diseases seem to be associated with risk of in-hospital mortality.
Transversal psoas muscle thickness measurement is associated with response and survival in patients with HCC undergoing immunotherapy
Authors: Scheiner Bernhard , Lampichler Katharina , Pomej Katharina , Beer Lucian , Balcar Lorenz , Sartoris Riccardo , Bouattour Mohamed , Sidali Sabrina , Trauner Michael , Mandorfer Mattias , Reiberger Thomas , Scharitzer Martina , Tamandl Dietmar , Pinato David J. , Ronot Maxime , Pinter Matthias
Published: September 2023

Background:

Sarcopenia is a common problem in patients with HCC. We aimed to evaluate the prognostic and predictive value of baseline transversal psoas muscle thickness (TPMT) measurement in patients with HCC undergoing immunotherapy.

Methods:

HCC patients treated with programmed death ligand 1–based therapies between June 2016 and October 2022 at the Vienna General Hospital (n = 80) and the Hôpital Beaujon Clichy (n = 96) were included and followed until April 2023. TPMT at the level of the third lumbar vertebra was measured independently by 2 radiologists to evaluate interreader reliability. TPMT <12 mm/m in men and <8 mm/m in women indicated sarcopenia.

Results:

Overall, 176 patients (age: 66.3±11.7 y; male: n=143, 81%, Barcelona-Clinic Liver Cancer C: n=121, 69%) were included, of which 131 (74%) exhibited cirrhosis. Interreader agreement for the diagnosis of sarcopenia based on TPMT was 92.6%, and Cohen κ showed a “strong agreement” [κ = 0.84 (95% CI: 0.75–0.92)]. Sarcopenia, present in 58 patients (33%), was associated with shorter median overall survival [7.2 (95% CI: 5.0–9.5) vs. 22.6 (95% CI: 16.4–28.8 months); p < 0.001] and median progression-free survival [3.4 (95% CI: 0.2–6.8) vs. 7.9 (95% CI: 5.8–9.9 months), p = 0.001], and an independent predictor of overall [adjusted HR: 1.63 (95% CI: 1.07–2.48)] and progression-free mortality [adjusted HR: 1.54 (95% CI: 1.06–2.23)] in multivariable analyses. The objective response rate [evaluable in 162 subjects (92.0%)] per modified Response Evaluation Criteria In Solid Tumors (mRECIST) in patients with and without sarcopenia was 22% and 39%, respectively (p = 0.029). Survival and radiological responses were worse in patients with sarcopenia and systemic inflammation [median overall survival: 6.1 (95% CI: 3.6–8.6) mo; median progression-free survival: 2.8 (95% CI: 2.1–3.4) mo; objective response rate=16%; disease control rate=39%].

Conclusions:

Evaluation of sarcopenia using TPMT measurement is reliable and identifies HCC patients with a dismal prognosis and response to immunotherapy.