bluuebunny/crossref_metadata_2025 huggingface dataset:
OMA orthology in 2024: improved prokaryote coverage, ancestral and extant GO enrichment, a revamped synteny viewer and more in the OMA Ecosystem
Authors: Altenhoff Adrian M , Warwick Vesztrocy Alex , Bernard Charles , Train Clement-Marie , Nicheperovich Alina , Prieto Baños Silvia , Julca Irene , Moi David , Nevers Yannis , Majidian Sina , Dessimoz Christophe , Glover Natasha M
Published: November 2023

In this update paper, we present the latest developments in the OMA browser knowledgebase, which aims to provide high-quality orthology inferences and facilitate the study of gene families, genomes and their evolution. First, we discuss the addition of new species in the database, particularly an expanded representation of prokaryotic species. The OMA browser now offers Ancestral Genome pages and an Ancestral Gene Order viewer, allowing users to explore the evolutionary history and gene content of ancestral genomes. We also introduce a revamped Local Synteny Viewer to compare genomic neighborhoods across both extant and ancestral genomes. Hierarchical Orthologous Groups (HOGs) are now annotated with Gene Ontology annotations, and users can easily perform extant or ancestral GO enrichments. Finally, we recap new tools in the OMA Ecosystem, including OMAmer for proteome mapping, OMArk for proteome quality assessment, OMAMO for model organism selection and Read2Tree for phylogenetic species tree construction from reads. These new features provide exciting opportunities for orthology analysis and comparative genomics. OMA is accessible at https://omabrowser.org.
Decoding complexity in biomolecular recognition of DNA i-motifs with microarrays
Authors: Yazdani Kamyar , Seshadri Srinath , Tillo Desiree , Yang Mo , Sibley Christopher D , Vinson Charles , Schneekloth John S
Published: November 2023

DNA i-motifs (iMs) are non-canonical C-rich secondary structures implicated in numerous cellular processes. Though iMs exist throughout the genome, our understanding of iM recognition by proteins or small molecules is limited to a few examples. We designed a DNA microarray containing 10976 genomic iM sequences to examine the binding profiles of four iM-binding proteins, mitoxantrone and the iMab antibody. iMab microarray screens demonstrated that pH 6.5, 5% BSA buffer was optimal, and fluorescence was correlated with iM C-tract length. hnRNP K broadly recognizes diverse iM sequences, favoring 3–5 cytosine repeats flanked by thymine-rich loops of 1–3 nucleotides. Array binding mirrored public ChIP-Seq datasets, in which 35% of well-bound array iMs are enriched in hnRNP K peaks. In contrast, other reported iM-binding proteins had weaker binding or preferred G-quadruplex (G4) sequences instead. Mitoxantrone broadly binds both shorter iMs and G4s, consistent with an intercalation mechanism. These results suggest that hnRNP K may play a role in iM-mediated regulation of gene expression in vivo, whereas hnRNP A1 and ASF/SF2 are possibly more selective in their binding preferences. This powerful approach represents the most comprehensive investigation of how biomolecules selectively recognize genomic iMs to date.
Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis
Authors: Weiner Daniel E , Schaufler Thilo , McCafferty Kieran , Kalantar-Zadeh Kamyar , Germain Michael , Ruessmann Despina , Morin Isabelle , Menzaghi Frédérique , Wen Warren , Ständer Sonja
Published: November 2023

Background

Poor sleep quality is associated with higher mortality and lower quality of life in patients with chronic kidney disease–associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis (HD). This post hoc analysis of the Phase 3 difelikefalin studies (Study 3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in individuals with CKD-aP improved sleep quality.

Methods

Itch intensity was assessed in patients undergoing HD who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1 and -2) or placebo (N = 425, KALM-1 and -2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D Itch Scale (5-D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS).

Results

Greater improvements in sleep quality were observed in patients with ≥3-point versus <3-point WI-NRS improvement using SQ-NRS in Study 3105 [mean (95% confidence interval) −5.2 (–5.6, −4.8) vs −1.5 (–2.0, −1.0)] and 5-D SDQ in KALM-1 and -2 [–1.8 (–2.1, −1.6) vs −0.8 (–1.1, −0.4)]. SQ-NRS and WI-NRS scores were highly correlated at both baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM-1 and -2.

Conclusions

In patients undergoing HD with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief.

Trial Registration

KALM-1 (NCT03422653), KALM-2 (NCT03636269), Study 3105 (NCT03998163).
Early progression of chronic histologic lesions in kidney transplant biopsies is not associated with HLA histocompatibility
Authors: Jabbour Rhea , Heinzel Andreas , Reindl-Schwaighofer Roman , Gregorich Mariella G , Regele Heinz , Kozakowski Nicolas , Kläger Johannes , Fischer Gottfried , Kainz Alexander , Becker Jan U , Wiebe Chris , Oberbauer Rainer
Published: November 2023

Background

Early progression of chronic histologic lesions in kidney allografts represents the main finding in graft attrition. The objective of this retrospective cohort study was to elucidate whether HLA histocompatibility is associated with progression of chronic histologic lesions in the first year post-transplant. Established associations of de novo donor-specific antibody (dnDSA) formation with HLA mismatch and microvascular inflammation (MVI) were calculated to allow for comparability with other study cohorts.

Methods

We included 117 adult kidney transplant recipients, transplanted between 2016 and 2020 from predominantly deceased donors, who had surveillance biopsies at 3 and 12 months. Histologic lesion scores were assessed according to the Banff classification. HLA mismatch scores [i.e. eplet, predicted indirectly recognizable HLA-epitopes algorithm (PIRCHE-II), HLA epitope mismatch algorithm (HLA-EMMA), HLA whole antigen A/B/DR] were calculated for all transplant pairs. Formation of dnDSAs was quantified by single antigen beads.

Results

More than one-third of patients exhibited a progression of chronic lesion scores by at least one Banff grade in tubular atrophy (ct), interstitial fibrosis (ci), arteriolar hyalinosis (ah) and inflammation in the area of interstitial fibrosis and tubular atrophy (i-IFTA) from the 3- to the 12-month biopsy. Multivariable proportional odds logistic regression models revealed no association of HLA mismatch scores with progression of histologic lesions, except for ah and especially HLA-EMMA DRB1 [odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.03–1.18]. Furthermore, the established associations of dnDSA formation with HLA mismatch and MVI (OR = 5.31, 95% CI 1.19–22.57) could be confirmed in our cohort.

Conclusions

These data support the association of HLA mismatch and alloimmune response, while suggesting that other factors contribute to early progression of chronic histologic lesions.
Anionic lipids facilitate membrane development and protochlorophyllide biosynthesis in etioplasts
Authors: Yoshihara Akiko , Kobayashi Keiko , Nagata Noriko , Fujii Sho , Wada Hajime , Kobayashi Koichi
Published: November 2023

Dark-germinated angiosperm seedlings develop chloroplast precursors called etioplasts in cotyledon cells. Etioplasts develop lattice membrane structures called prolamellar bodies (PLBs), where the chlorophyll intermediate protochlorophyllide (Pchlide) forms a ternary complex with NADPH and light-dependent NADPH:Pchlide oxidoreductase (LPOR). The lipid bilayers of etioplast membranes are mainly composed of galactolipids, which play important roles in membrane-associated processes in etioplasts. Although etioplast membranes also contain 2 anionic lipids, phosphatidylglycerol (PG) and sulfoquinovosyldiacylglycerol (SQDG), their roles are unknown. To determine the roles of PG and SQDG in etioplast development, we characterized etiolated Arabidopsis (Arabidopsis thaliana) mutants deficient in PG and SQDG biosynthesis. A partial deficiency in PG biosynthesis loosened the lattice structure of PLBs and impaired the insertion of Mg2+ into protoporphyrin IX, leading to a substantial decrease in Pchlide content. Although a complete lack of SQDG biosynthesis did not notably affect PLB formation and Pchlide biosynthesis, lack of SQDG in addition to partial PG deficiency strongly impaired these processes. These results suggested that PG is required for PLB formation and Pchlide biosynthesis, whereas SQDG plays an auxiliary role in these processes. Notably, PG deficiency and lack of SQDG oppositely affected the dynamics of LPOR complexes after photoconversion, suggesting different involvements of PG and SQDG in LPOR complex organization. Our data demonstrate pleiotropic roles of anionic lipids in etioplast development.
Chloroplast phosphate transporter CrPHT4-7 regulates phosphate homeostasis and photosynthesis in Chlamydomonas
Authors: Tóth Dávid , Kuntam Soujanya , Ferenczi Áron , Vidal-Meireles André , Kovács László , Wang Lianyong , Sarkadi Zsuzsa , Migh Ede , Szentmihályi Klára , Tengölics Roland , Neupert Juliane , Bock Ralph , Jonikas Martin C , Molnar Attila , Tóth Szilvia Z
Published: November 2023

In eukaryotic cells, phosphorus is assimilated and utilized primarily as phosphate (Pi). Pi homeostasis is mediated by transporters that have not yet been adequately characterized in green algae. This study reports on PHOSPHATE TRANSPORTER 4-7 (CrPHT4-7) from Chlamydomonas reinhardtii, a member of the PHT4 transporter family, which exhibits remarkable similarity to AtPHT4;4 from Arabidopsis (Arabidopsis thaliana), a chloroplastic ascorbate transporter. Using fluorescent protein tagging, we show that CrPHT4-7 resides in the chloroplast envelope membrane. Crpht4-7 mutants, generated by the CRISPR/Cas12a-mediated single-strand templated repair, show retarded growth, especially in high light, reduced ATP level, strong ascorbate accumulation, and diminished non-photochemical quenching in high light. On the other hand, total cellular phosphorous content was unaffected, and the phenotype of the Crpht4-7 mutants could not be alleviated by ample Pi supply. CrPHT4-7-overexpressing lines exhibit enhanced biomass accumulation under high light conditions in comparison with the wild-type strain. Expressing CrPHT4-7 in a yeast (Saccharomyces cerevisiae) strain lacking Pi transporters substantially recovered its slow growth phenotype, demonstrating that CrPHT4-7 transports Pi. Even though CrPHT4-7 shows a high degree of similarity to AtPHT4;4, it does not display any substantial ascorbate transport activity in yeast or intact algal cells. Thus, the results demonstrate that CrPHT4-7 functions as a chloroplastic Pi transporter essential for maintaining Pi homeostasis and photosynthesis in C. reinhardtii.
Branching in molecular structure enhancement of solubility in CO2
Authors: Kobayashi Kazuya , Firoozabadi Abbas
Published: November 2023

Most compounds of some 1,000 amu molecular weight (MW) and higher are poorly soluble in carbon dioxide (CO2). Only at very high pressure, there may be mild solubility. This limits the use of CO2 as a solvent and modifications of CO2 properties through additives. We have developed a coarse-grained molecular model to investigate the dependency of the solubility of hydrocarbon oligomers (MW of ∼1,000 amu) in CO2 and on the molecular structure. The coarse-grained model is optimized by the particle swarm optimization algorithm to reproduce density, surface tension, and enthalpy of vaporization of a highly branched hydrocarbon oligomer (poly-1-decene with six repeating units). We demonstrate that branching in molecular structure of oligomers significantly increases solubility in CO2. The branching in molecular structure results in up to 270-time enhancement of solubility in CO2 than an n-alkane with the same MW. The number of structural edges (methyl group) is a key in improved CO2-philicity. The solubility of poly-1-decene with nine repeating units (MW of 1,264.4 amu) is higher in CO2 than poly-1-dodecene with six repeating units (MW of 1,011.93 amu) because it has more structural edges (10 vs. 7). These results shed light on the enhancement of CO2-philicity by altering molecular structure rather than modifying chemical composition in compounds.
Sources of Inconsistency in the Measurement of Religious Affiliation: Evidence from a Survey Experiment and Cognitive Interviews
Authors: Brenner Philip S , LaPlante Jill , Reed Tracy L
Published: November 2023

Research has argued that estimates of the percentage of Americans without a religious affiliation may be influenced by a measurement artifact caused by the poor reliability of conventional survey questions. Using a question-order experiment and cognitive interviews, we assess religious affiliation measures like those commonly used on surveys. A filter question and a full question presenting a list of religious affiliations as response options are asked in a random order. Findings suggest that nominally religious respondents have higher odds of reporting an affiliation to the full question than the filter. They describe nominal or residual religious affiliations, highlighting the role of family connections and religious pasts in their affiliation reports. Conversely, highly religious and nonreligious respondents are, respectively, only slightly and not at all influenced by question characteristics. Findings suggest that using a filter question before a full question avoids this source of inconsistency and yields better data quality.
Steroid receptor coactivator‐2 drives epithelial reprogramming that enables murine embryo implantation
Authors: Maurya Vineet K. , Szwarc Maria M. , Lonard David M. , Kommagani Ramakrishna , Wu San Pin , O'Malley Bert W. , DeMayo Francesco J. , Lydon John P.
Published: November 2023

Although we have shown that steroid receptor coactivator‐2 (SRC‐2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC‐2's role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC‐2 knockout mouse (SRC‐2d/d) in timed natural pregnancy studies, we show that endometrial SRC‐2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E‐cadherin on the apical surface and basolateral adherens junctions of the SRC‐2d/d luminal epithelium, respectively. These findings indicate that the SRC‐2d/d luminal epithelium fails to exhibit a plasma membrane transformation (PMT) state known to be required for the development of uterine receptivity. Transcriptomics demonstrated that the expression of genes involved in steroid hormone control of uterine receptivity were significantly disrupted in the SRC‐2d/d endometrium as well as genes that control epithelial tight junctional biology and the emergence of the epithelial mesenchymal transition state, with the latter sharing similar biological properties with PMT. Collectively, these findings uncover a new role for endometrial SRC‐2 in the induction of the luminal epithelial PMT state, which is a prerequisite for the development of uterine receptivity and early pregnancy establishment.
SARS-CoV-2 vaccination in primary antibody deficiencies: an overview on efficacy, immunogenicity, durability of immune response and safety
Authors: Cusa Gabriella , Sardella Germano , Garzi Giulia , Firinu Davide , Milito Cinzia
Published: November 2023

Purpose of review

This review aims to summarize the current best knowledge on the efficacy of COVID-19 vaccination in vulnerable patients affected by primary antibody deficiencies (PADs), both in patients previously infected and vaccine-immunized, focusing also on the durability, on the need for multiple booster doses and on the safety of anti-SARS-CoV-2 vaccines.

Recent findings

Patients vaccinated for SARS-CoV2 have variable humoral response, still showing a tendency towards an increase in antibody titers, with factors such as booster doses, previous infections, age and specific genetic mutations influencing the outcome. Long-lasting cellular responses to SARS-CoV-2 vaccination instead, mostly of the T-cell type, have been observed. Overall, the duration of protection given by vaccinations is sufficient and increased upon further simulations. Furthermore, the safety profile in PID patients is excellent, with most adverse events being transient and mild and no major adverse event reported.

Several studies have emphasized the benefit of vaccinating patients with PADs against the SARS-CoV-2 virus and the necessity of administering booster doses. This review, by gathering the most recent and significant data from the scientific literature, could be helpful in clinical practice in the management of disease prevention in patients affected by primary immunodeficiency and also serve as inspiration for further in-depth clinical research.
Needs of Women Caring for Husbands with Cancer at Cancer Diseases Hospital in Lusaka, Zambia: An Analytical Nonintervention, Cross-Sectional Survey
Authors: Mbozi Patience , Mukwato Patricia K. , Kalusopa Victoria M. , Simoonga Christopher
Published: November 2023

Background:

The number of men with cancer at the Cancer Diseases Hospital (CDH) in Zambia has nearly doubled. The CDH offers free treatment, but the families pay for “extras”, for example, laboratory and diagnostic investigations.

Objective:

To assess the needs of women caring for their husbands with cancer at the CDH.

Methods:

Stratified random sampling was used for this cross-sectional survey. Data were collected using a 27-item Needs Assessment of Family Caregivers-Cancer tool; analysis used SPSS version 23 and STATA version 17. Women currently caring for their husbands with cancer or in follow-up at the CDH and able to read/write English were eligible.

Results:

A statistically significant association was found between wives’ ability to pay husbands’ medical fees and education, cancer diagnosis and stage, and occupation and income. Emotional distress was associated with taking time for herself and family gatherings. Statistically significant factors for improving emotional distress were satisfaction with hospital staff help, medical insurance, and managing husbands’ pain and symptoms.

Conclusions:

Women’s financial resources directly impacted their husbands’ care. When 4 specific needs were met, the women’s emotional distress was low.

Implications for Practice:

Nurses must acknowledge the impact of husbands’ cancer on wives and assess their needs to execute appropriate supportive interventions throughout their caring journey.

What is Foundational:

Women caring for husbands with cancer shared their caring experiences, emotional distress, and coping. The findings inform further research on how CDH nurses can best support these critical caregivers with a larger care role due to shortages of professional support personnel.
Incorporating Efficacy Data from Initial Trials Into Subsequent Evaluations: Application to Vaccines Against Respiratory Syncytial Virus
Authors: Warren Joshua L. , Sundaram Maria , Pitzer Virginia E. , Omer Saad B. , Weinberger Daniel M.
Published: November 2023

Background:

When a randomized controlled trial fails to demonstrate statistically significant efficacy against the primary endpoint, a potentially costly new trial would need to be conducted to receive licensure. Incorporating data from previous trials might allow for more efficient follow-up trials to demonstrate efficacy, speeding the availability of effective vaccines.

Methods:

Based on the outcomes from a failed trial of a maternal vaccine against respiratory syncytial virus (RSV), we simulated data for a new Bayesian group-sequential trial. We analyzed the data either ignoring data from the previous trial (i.e., weakly informative prior distributions) or using prior distributions incorporating the historical data into the analysis. We evaluated scenarios where efficacy in the new trial was the same, greater than, or less than that in the original trial. For each scenario, we evaluated the statistical power and type I error rate for estimating the vaccine effect following interim analyses.

Results:

When we used a stringent threshold to control the type I error rate, analyses incorporating historical data had a small advantage over trials that did not. If control of type I error is less important (e.g., in a postlicensure evaluation), the incorporation of historical data can provide a substantial boost in efficiency.

Conclusions:

Due to the need to control the type I error rate in trials used to license a vaccine, incorporating historical data provides little additional benefit in terms of stopping the trial early. However, these statistical approaches could be promising in evaluations that use real-world evidence following licensure.
Epidural analgesia versus oral morphine for postoperative pain management following video-assisted thoracic surgery
Authors: Holm Jimmy H. , Andersen Claus , Toft Palle
Published: November 2023

BACKGROUND

The use of thoracic epidural analgesia for postoperative pain management in video-assisted thoracic surgery (VATS) is controversial. Still, the evidence on omitting it in favour of systemic opioids is inconclusive, and studies are small and non-blinded.

OBJECTIVE

We aimed to compare pain after VATS using epidural analgesia or enteral opioids for postoperative pain management.

DESIGN/SETTING/PATIENTS/INTERVENTION

A randomised, double-blind, controlled trial at a Danish tertiary hospital. Adult patients scheduled for VATS were assigned to multimodal non-opioid baseline analgesia supplemented with either thoracic epidural analgesia (TE Group) or oral morphine (OM Group) for postoperative pain management. We recorded pain five times a day, both at rest and during activity, using the Numeric Rating Scale (NRS) and categorised it into “acceptable pain” or “unacceptable pain”. Unacceptable pain was defined as NRS (at rest) ≥3 or NRS (with activity) ≥5 when supplementary analgesics were given.

MAIN OUTCOME MEASURES

The primary outcomes were the proportions of patients experiencing “unacceptable pain” during the postoperative period and the use of intravenous “rescue” opioids.

RESULTS

Of the 161 included patients, 146 received the allocated treatment and their data were analysed. At rest, 34% of patients in the TE Group and 64% of patients in the OM Group experienced unacceptable pain during the study period, a significant between-group difference of 30% (P < 0.0005). During activity these percentages were 32% of patients in the TE Group and 59% in the OM group, a difference of 27% (P < 0.005). The median intravenous rescue morphine consumption during the study period was 4.5 [interquartile range (IQR), 0–10.0] mg in the TE Group and 7.5 [0–19.0] mg in the OM Group (P < 0.005).

CONCLUSION

Epidural analgesia provided better pain relief after VATS than oral morphine. The between-group difference in rescue intravenous morphine consumption was statistically significant but clinically irrelevant.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT02359175).
Videolaryngoscopy use before and after the initial phases of the COVID-19 pandemic
Authors: Wylie Nia W. , Durrant Emma L. , Phillips Emma C. , De Jong Audrey , Schoettker Patrick , Kawagoe Izumi , de Pinho Martins Márcio , Zapatero Juliana , Graham Catriona , McNarry Alistair F. ,   the VL-iCUE Group∗
Published: November 2023

BACKGROUND

The potential benefit of videolaryngoscopy use in facilitating tracheal intubation has already been established, however its use was actively encouraged during the COVID-19 pandemic as it was likely to improve intubation success and increase the patient-operator distance.

OBJECTIVES

We sought to establish videolaryngoscopy use before and after the early phases of the pandemic, whether institutions had acquired new devices during the COVID-19 pandemic, and whether there had been teaching on the devices acquired.

DESIGN

We designed a survey with 27 questions made available via the Joint Information Scientific Committee JISC online survey platform in English, French, Spanish, Chinese, Japanese and Portuguese. This was distributed through 18 anaesthetic and airway management societies.

SETTING

The survey was open for 54 to 90 days in various countries. The first responses were logged on the databases on 28 October 2021, with all databases closed on 26 January 2022. Reminders to participate were sent at the discretion of the administering organisations.

PARTICIPANTS

All anaesthetists and airway managers who received the study were eligible to participate.

MAIN OUTCOME MEASURES

Videolaryngoscopy use before the COVID-19 pandemic and at the time of the survey.

RESULTS

We received 4392 responses from 96 countries: 944/4336 (21.7%) were from trainees. Of the 3394 consultants, 70.8% (2402/3394) indicated no change in videolaryngoscopy use, 19.9% (675/3394) increased use and 9.3% (315/3393) reduced use. Among trainees 65.5% (618/943) reported no change in videolaryngoscopy use, 27.7% (261/943) increased use and 6.8% (64/943) reduced use. Overall, videolaryngoscope use increased by 10 absolute percentage points following the pandemic.

CONCLUSIONS

Videolaryngoscopy use increased following the early phase of the COVID-19 pandemic but this was less than might have been expected.
Cytochrome P4503A4 gene polymorphisms guide safe sufentanil analgesic doses in pregnant Chinese mothers: a multicenter, randomized, prospective study
Authors: Shu Xiangrong , Yan Yan , Yu Jingxian , Chi Liqun
Published: November 2023

Background

Sufentanil and ropivacaine when used as epidural anesthetics effectively reduce maternal pain during labor. From previous reports,rs2242480single nucleotide polymorphisms (SNPs) can alter sufentanil metabolism, which affects analgesic efficacy.

Methods

We randomly divided 573 eligible mothers into groups A and B (in a 1 : 3 ratio). The control group (group A) was given sufentanil at the usual 0.5 mg/L-1dose + 0.15% ropivacaine hydrochloride mixture in 10 ml. The sufentanil dose given to the intervention group (group B) was determined by genotype: the GA and AA genotype group (group B1) was given 87.6% (design based on previous study results) of the usual sufentanil clinical dose (0.438 mg/L-1sufentanil + 0.15% ropivacaine hydrochloride mixture in 10 ml) and the GG genotype group (group B2) was given the same dose as group A. Efficacy indicators consisting of maternal vital signs, obstetric transfer, neonatal prognostic indicators, and adverse effects were recorded before and after analgesia across groups.

Results

Visual analog scale scores after analgesia across groups were significantly different from scores before analgesia, showing that analgesic effects across groups were effective. No significant differences were observed in efficacy, obstetric transfer, and neonatal prognosis indicators between groups. In comparison to groups B1 and B2, group A showed more markedly suppressed cardiovascular and respiratory effects, and also a higher incidence of negative side effects such as vomiting and urinary retention.

Conclusion

We confirmed that individualizing sufentanil doses based on maternal genotypes increased safety and success rates for women during childbirth.
General Principles for Counseling and Management of Triplet Pregnancies
Authors: Mhatre Mohak , Craigo Sabrina
Published: November 2023

Compared with singleton pregnancies, triplet pregnancies are associated with a significantly increased risk of adverse pregnancy outcomes. Early ultrasound examination is the best way to diagnose triplets, establish dating, and determine the number of placentas to provide appropriate counseling and monitoring. Dichorionic placentation adds risks specifically associated with a shared placenta, and limits options for intervention. Multifetal reduction is an option that can significantly improve pregnancy outcomes compared with non-reduced triplet pregnancies. Integration of a Maternal-Fetal Medicine specialist in the prenatal care for a triplet pregnancy reduces the risk of preeclampsia, preterm birth, low birthweight infants, perinatal mortality, and major neonatal morbidity.
NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas
Authors: Castro-Trujillo Sebastián , Segura Katherine , Bolívar-Marín Sara , Salgado Doris M. , Bosch Irene , Vega Rocío , Rojas María Clemencia , Narváez Carlos F.
Published: November 2023

Background:

Infections by dengue virus (DENV) and Zika virus (ZIKV) have some similar symptoms and a cross-reactive immune response, although with different risk populations and outcomes. Here, we evaluated the virologic characteristics and the nonstructural protein 1 (NS1)-specific antibody responses to DENV and ZIKV in children suspected of dengue in different epidemiologic moments in Colombia.

Methods:

Viral RNA, circulating NS1 and IgM/IgG specific for DENV and ZIKV were performed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) in 301 children suspected of dengue enrolled in a hospital setting during the ZIKV epidemic and a primary healthcare setting during a DENV epidemic. For the detection of DENV and ZIKV-specific IgM, an NS1-based ELISA was validated using characterized pediatric samples. Clinical and laboratory parameters were also evaluated.

Results:

DENV RNA or NS1 antigen was detected in the plasma of 62% of children, and in none, the ZIKV RNA was found. NS1-based ELISA for DENV and ZIKV IgM showed a sensitivity/specificity of 90/84% and 73/98%, respectively. Of 114 children without detectable viremia or antigenemia, 30.7%, 17.5%, 22% and 30% were IgM-DENV+, IgM-ZIKV+, IgM-DENV+ZIKV+ and IgM-DENV-ZIKV-, respectively. The ZIKV/DENV IgM-NS1 ratio allows the identification of the infecting orthoflavivirus in 88% of the children with IgM-DENV+ZIKV+, confirming a high predominance of DENV infections in the 2 pediatric settings.

Conclusion:

Overall, 88% of the children with clinical suspicion of dengue had an identifiable orthoflaviviral infection, with 80% caused by DENV, 7% by ZIKV and 0.7% classified as recent infections or coinfection, demonstrating active viral cocirculation in the pediatric population of southern Colombia. The IgM-NS1 detection improved the identification of orthoflaviviral infections in children without viremia or antigenemia, suggesting it is a helpful complementary tool for medical personnel in tropical regions with high viral cocirculation and different clinical scenes.
Giardia lamblia Diagnosed During Upper Gastrointestinal Endoscopy: Clinical Manifestation, Histopathologic Findings and the Association With Celiac Disease
Authors: Hoofien Assaf , Kori Michal
Published: November 2023

Background:

Giardia lamblia may be found incidentally during upper gastrointestinal (GI) endoscopy, including when biopsies are taken for celiac disease (CeD) diagnosis. We aimed to study the clinical presentation and histopathology of G. lamblia and determine its association with CeD.

Methods:

A retrospective case series of pediatric patients diagnosed with G. lamblia based on intestinal biopsies between January 1999 and January 2023. Baseline data; demographics, symptoms, celiac serology, stool testing, macroscopic and histopathologic findings. Follow-up data; treatment and repeated celiac serology.

Results:

Of 38 patients with G. lamblia, 15 (39.5%) were female, mean age of 6.7 (±4.8 SD) years. Clinical symptoms; GI 19/38 (50%), growth retardation and/or iron deficiency anemia 8/38 (21.1%) or a combination 11/38 (28.9%). Celiac serology was positive in 13/38 (34.2%). Duodenal endoscopic findings; normal (n = 23, 60.5%), nodularity (n = 12, 32.4%), erosions in 2 (5.4%) and scalloping in 1 (2.7%). Histopathology; normal villi 24/38 (63.2%), villous shortening with increased intraepithelial lymphocytes (IEL) 5/38 (13.2%), isolated IEL 3/38 (7.9%) and duodenitis in 6/38 (15.8%). Children with positive CeD serology were younger (4 vs. 8.1 years, P = 0.019), had fewer GI symptoms (23.1% vs. 64%, P = 0.017) and a higher rate of villous shortening with increased IEL (38.5% vs. 0, P < 0.001) versus children with negative serology. On follow-up, metronidazole treatment was recommended to all but was documented to be given in 22/38 (57.9%). Among the 13 children with positive CeD serology, serology normalized in 10 (77%).

Conclusions:

G. lamblia is a rare histopathologic finding in children. It may be an incidental finding in CeD or may cause false positive celiac serology.
Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell
Authors: Kelley Abigail M. , Del Valle Eric J. , Zaman Samin , Karkhanis Anushree N.
Published: November 2023

Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder. Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. Therefore, in this project, we investigated the impact of adolescent chronic intermittent ethanol (aCIE) exposure on mechanical allodynia. Furthermore, given the involvement of the NAc shell in pain processing and chronic ethanol-mediated changes, we measured changes in accumbal dopamine kinetics during protracted withdrawal. We found that both male and female aCIE rats show mechanical allodynia during withdrawal. Furthermore, male and female aCIE rats show greater evoked tonic dopamine release, maximal rate of dopamine reuptake, and dopamine affinity to the dopamine transporter in the NAc shell compared with controls. With phasic stimulation, aCIE rats also showed greater dopamine release compared with AIR-exposed rats. Inhibition of dopamine transmission targeted in the NAc shell reversed the aCIE-associated facilitation of mechanical allodynia in both sexes. These data suggest that aCIE exposure exacerbates pain sensitivity during withdrawal in an accumbal dopamine-dependent manner.
The Influence of Patient Care, Shadowing, and Volunteer Experience on Diverse Applicant Matriculation Into Physician Assistant/Associate Programs
Authors: Bruza-Augatis Mirela , Coplan Bettie , Sethi Wendiann , McDaniel M. Jane
Published: November 2023

Introduction

To better understand factors contributing to low matriculation rates for health professions students from backgrounds underrepresented in medicine (URiM), this study examined the influence of healthcare-releated preadmission experiences on physician assistant/associate (PA) program matriculation.

Methods

We analyzed data from the Centralized Application Service for PAs 2018 to 2019 admissions cycle to compare characteristics of non-URiM and URiM PA program applicants and matriculants. The primary focus was on preadmission healthcare-releated experiences. To control for the strong influence of grade point average (GPA) on the likelihood of matriculation, we divided applicants into 2 groups: those with GPA < 3.6 (the median GPA for matriculants) and those with GPA ≥ 3.6. Analyses consisted of descriptive statistics and logistic regressions.

Results

Our sample consisted of 25,880 PA program applicants. Higher proportions of URiM compared with non-URiM applicants identified as first-generation college students (39.3% vs. 19.9%) or indicated economic disadvantage (32.3% vs. 12.5%). Overall, higher proportions of URiM compared with non-URiM applicants reported no patient care experience (24.3% vs. 17.9%), no shadowing (31.7% vs. 21.7%), or no volunteering (32.2% vs. 26.9%). Among all applicants with GPA < 3.6, reporting any type of experience was associated with increased odds of matriculation. Among URiM applicants with GPA ≥ 3.6, patient care experience did not influence odds of matriculation (odds ratio [OR] = 1.22, P = .23), whereas shadowing was associated with twice the odds (OR = 2.01, P < .001).

Discussion

Although academic metrics are known to predict PA program matriculation, we found that preadmission experiences also play a role. The study findings suggest that lack of experience hours may hinder URiM student access to PA education.
Nurse practitioner satisfaction with in-person versus telehealth chronic care delivery
Authors: Ibemere Stephanie O. , Silva Susan G. , Affronti Mary Lou , Masese Rita , Tanabe Paula
Published: November 2023

Background:

The widespread use of telehealth and regulatory changes that enhanced nurse practitioner (NP) practice authority because of the SARS-CoV-2 pandemic offers an opportunity to assess postpandemic NP satisfaction with telehealth care delivery and perceptions of its feasibility compared with in-person visits.

Purpose:

Outpatient chronic care delivery satisfaction and preference were compared among NPs who provide care to adults through in-person and/or telehealth visits and examined NP demographic and clinical characteristics associated with overall satisfaction by care delivery type.

Methodology:

Data were collected using a cross-sectional, descriptive design through online dissemination of The Care Delivery Satisfaction Survey to a nationally representative sample of 586 NPs.

Results:

Compared with NPs using both visit types to deliver care, NPs delivering care in-person only had significantly lower satisfaction scores for interpersonal manner (p = .0076) and communication (p = .0108). NPs using telehealth only had significantly higher overall satisfaction and satisfaction subscale scores (all p < .01) compared with NPs using both visit types. Overall, 77% of NPs using both visit types preferred in-person delivery.

Conclusions/Implications:

NPs delivering telehealth care only were more satisfied with chronic care delivery than NPs using both delivery types. NPs using both types were more satisfied with interpersonal manner and communication compared with NPs delivering in-person care only. Most NPs using both types preferred in-person care delivery. Given increased telehealth use, health systems, academic institutions, and insurance companies can use these study findings to inform policy on telehealth resources and infrastructure.
Linking Medicare-Medicaid Claims for Patient-Centered Outcomes Research Among Dual-Eligible Beneficiaries
Authors: Jones Kelley A. , Clark Amy G. , Greiner Melissa A. , Sandoe Emma , Giri Abhigya , Hammill Bradley G. , Van Houtven Courtney H. , Higgins Aparna , Kaufman Brystana
Published: November 2023

Background:

Evaluation of Medicare-Medicaid integration models’ effects on patient-centered outcomes and costs requires multiple data sources and validated processes for linkage and reconciliation.

Objective:

To describe the opportunities and limitations of linking state-specific Medicaid and Centers for Medicare & Medicaid Services administrative claims data to measure patient-centered outcomes for North Carolina dual-eligible beneficiaries.

Research Design:

We developed systematic processes to (1) validate the beneficiary ID linkage using sex and date of birth in a beneficiary ID crosswalk, (2) verify dates of dual enrollment, and (3) reconcile Medicare-Medicaid claims data to support the development and use of patient-centered outcomes in linked data.

Participants:

North Carolina Medicaid beneficiaries with full Medicaid benefits and concurrent Medicare enrollment (FBDE) between 2014 and 2017.

Measures:

We identified need-based subgroups based on service use and eligibility program requirements. We calculated utilization and costs for Medicaid and Medicare, matched Medicaid claims to Medicare service categories where possible, and reported outcomes by the payer. Some services were covered only by Medicaid or Medicare, including Medicaid-only covered home and community-based services (HCBS).

Results:

Of 498,030 potential dual enrollees, we verified the linkage and FBDE eligibility of 425,664 (85.5%) beneficiaries, including 281,174 adults enrolled in Medicaid and Medicare fee-for-service. The most common need-based subgroups were intensive behavioral health service users (26.2%) and HCBS users (10.8%) for adults under age 65, and HCBS users (20.6%) and nursing home residents (12.4%) for adults age 65 and over. Medicaid funded 42% and 49% of spending for adults under 65 and adults 65 and older, respectively. Adults under 65 had greater behavioral health service utilization but less skilled nursing facility, HCBS, and home health utilization compared with adults 65 and older.

Conclusions:

Linkage of Medicare-Medicaid data improves understanding of patient-centered outcomes among FBDE by combining Medicare-funded acute and ambulatory services with Medicaid-funded HCBS. Using linked Medicare-Medicaid data illustrates the diverse patient experience within FBDE beneficiaries, which is key to informing patient-centered outcomes, developing and evaluating integrated Medicare and Medicaid programs, and promoting health equity.
Patterns of Morbidity Across the Lifespan
Authors: Lemke Klaus W. , Forrest Christopher B. , Leff Bruce A. , Boyd Cynthia M. , Gudzune Kimberly A. , Pollack Craig E. , Pandya Chintan J. , Weiner Jonathan P.
Published: November 2023

Background:

Classification systems to segment such patients into subgroups for purposes of care management and population analytics should balance administrative simplicity with clinical meaning and measurement precision.

Objective:

To describe and empirically apply a new clinically relevant population segmentation framework applicable to all payers and all ages across the lifespan.

Research Design and Subjects:

Cross-sectional analyses using insurance claims database for 3.31 Million commercially insured and 1.05 Million Medicaid enrollees under 65 years old; and 5.27 Million Medicare fee-for-service beneficiaries aged 65 and older.

Measures:

The “Patient Need Groups” (PNGs) framework, we developed, classifies each person within the entire 0–100+ aged population into one of 11 mutually exclusive need-based categories. For each PNG segment, we documented a range of clinical and resource endpoints, including health care resource use, avoidable emergency department visits, hospitalizations, behavioral health conditions, and social need factors.

Results:

The PNG categories included: (1) nonuser; (2) low-need child; (3) low-need adult; (4) low-complexity multimorbidity; (5) medium-complexity multimorbidity; (6) low-complexity pregnancy; (7) high-complexity pregnancy; (8) dominant psychiatric/behavioral condition; (9) dominant major chronic condition; (10) high-complexity multimorbidity; and (11) frailty. Each PNG evidenced a characteristic age-related trajectory across the full lifespan. In addition to offering clinically cogent groupings, large percentages (29%–62%) of patients in two pregnancy and high-complexity multimorbidity and frailty PNGs were in a high-risk subgroup (upper 10%) of potential future health care utilization.

Conclusions:

The PNG population segmentation approach represents a comprehensive measurement framework that captures and categorizes available electronic health care data to characterize individuals of all ages based on their needs.
Avenues for Strengthening PCORnet’s Capacity to Advance Patient-Centered Economic Outcomes in Patient-Centered Outcomes Research (PCOR)
Authors: Waitman Lemuel R. , Bailey Leonard Charles , Becich Michael J. , Chung-Bridges Katherine , Dusetzina Stacie B. , Espino Jessi U. , Hogan William R. , Kaushal Rainu , McClay James C. , Merritt James Greg , Rothman Russell L. , Shenkman Elizabeth A. , Song Xing , Nauman Elizabeth
Published: November 2023

PCORnet, the National Patient-Centered Clinical Research Network, provides the ability to conduct prospective and observational pragmatic research by leveraging standardized, curated electronic health records data together with patient and stakeholder engagement. PCORnet is funded by the Patient-Centered Outcomes Research Institute (PCORI) and is composed of 8 Clinical Research Networks that incorporate at total of 79 health system “sites.” As the network developed, linkage to commercial health plans, federal insurance claims, disease registries, and other data resources demonstrated the value in extending the networks infrastructure to provide a more complete representation of patient’s health and lived experiences. Initially, PCORnet studies avoided direct economic comparative effectiveness as a topic. However, PCORI’s authorizing law was amended in 2019 to allow studies to incorporate patient-centered economic outcomes in primary research aims. With PCORI’s expanded scope and PCORnet’s phase 3 beginning in January 2022, there are opportunities to strengthen the network’s ability to support economic patient-centered outcomes research. This commentary will discuss approaches that have been incorporated to date by the network and point to opportunities for the network to incorporate economic variables for analysis, informed by patient and stakeholder perspectives. Topics addressed include: (1) data linkage infrastructure; (2) commercial health plan partnerships; (3) Medicare and Medicaid linkage; (4) health system billing-based benchmarking; (5) area-level measures; (6) individual-level measures; (7) pharmacy benefits and retail pharmacy data; and (8) the importance of transparency and engagement while addressing the biases inherent in linking real-world data sources.
Usual Source of Care and Contraceptive Use
Authors: Wells Rebecca , Smith Nicole K.
Published: November 2023

Background:

A high proportion of people in the United States at risk of unintended pregnancy also have limited primary care access.

Study Design:

We pooled data for analyses from separate 2015–2017 and 2017–2019 waves of the National Survey of Family Growth. Multivariable logistic regression was used to estimate associations between the usual source of health care and self-reported use of a comprehensive range of contraceptive options, as well as alignment between patient preference and the current method.

Results:

Compared with having a private doctor or Health Maintenance Organization, not having a usual source of care was associated with lower odds of using short-term hormonal methods (OR=0.54, 95% CI: 0.40–0.73, for an 11 percentage point lower rate); higher odds of using time-based methods (OR=1.47, 95% CI: 1.10–1.97, for a 6 percentage point higher rate); and higher odds of preferring a contraceptive method other than the one most recently used (OR=1.39, 95% CI: 1.01–1.90, for a 6 percentage point higher probability). Reliance on an emergency department as a usual source of care was not associated with contraceptive use or satisfaction with the method used. Reliance on urgent care was associated only with higher odds of using time-based methods (OR=1.60, 95% CI: 1.03–2.50, for a 7 percentage point higher rate). Clinic-based usual care was not associated with any differences in contraceptive use but was associated with preferring a contraceptive method other than the one most recently used (OR=1.65, 95% CI: 1.21–2.25, for an 8 percentage point higher probability).

Conclusions.

All sources of usual care can improve contraceptive access.