bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Valbenazine in Japanese Patients With Tardive Dyskinesia and Schizophrenia/Schizoaffective Disorder or Bipolar Disorder/Depressive Disorder
Authors: Nagano Mieko , Susuta Yutaka , Masui Hideaki , Watanabe Yumi , Watanabe Koichiro
Published: February 2024

Purpose

This post hoc analysis investigated whether a patient's underlying psychiatric disease (schizophrenia/schizoaffective disorder [SCHZ] or bipolar disorder/depressive disorder [MOOD]) influenced the efficacy or safety of valbenazine for tardive dyskinesia (TD) in an Asian population.

Methods

We analyzed data from J-KINECT, a multicenter, phase II/III, randomized, double-blind study, which consisted of a 6-week placebo-controlled period followed by a 42-week extension where Japanese patients with TD received once-daily 40- or 80-mg valbenazine. We compared the change from baseline in Abnormal Involuntary Movement Scale total score and Clinical Global Impression of TD score between patients with SCHZ and those with MOOD, and incidence of treatment-emergent adverse events.

Results

Of 256 patients included in the placebo-controlled period, 211 continued to the long-term extension. The mean change from baseline in Abnormal Involuntary Movement Scale total score at week 6 (95% confidence interval) was −1.8 (−3.2 to −0.5) and −3.3 (−4.7 to −1.9) in the valbenazine 40- and 80-mg groups, respectively (SCHZ group), and −2.4 (−3.9 to −0.9) and −3.5 (−5.1 to −1.9) in the valbenazine 40- and 80-mg groups, respectively (MOOD group), demonstrating improvement at either dose level over placebo, regardless of the underlying disease. These results were maintained to week 48, and improvements of Clinical Global Impression of TD scores were similar. There were no notable differences in the incidence of serious or fatal treatment-emergent adverse events by underlying disease; differences in the incidence of worsening schizophrenia and depression were attributed to underlying disease progression.

Conclusions

Safety and efficacy of long-term valbenazine therapy for TD did not vary according to underlying psychiatric disease.
“I Hate Sim!”—Using Psychotherapeutic Concepts to Help Educators Attend to Challenging States of Mind During Simulation Prebriefs
Authors: Drake Gareth , Drewek Katherine
Published: February 2024

Summary Statement

This article outlines the theoretical development of an approach to simulation prebriefing that we have adopted at Great Ormond Street Children's Hospital. Many educators struggle with anxious or reticent learners during simulation. This reticence often becomes apparent first during the simulation prebrief. Previous work highlights key points to cover in a prebrief. Less work has been done on the dilemma of how to engage such learners while also attempting to maintain a pedagogically effective stance for the entire group. This article pulls together current best practice guidance on prebriefing before exploring pertinent concepts from psychotherapeutic and pedagogical domains—the therapeutic setting, the therapeutic stance, and epistemic trust—which we believe can usefully and practically be applied to simulation practice in the service of engaging reticent learners while enhancing the psychological safety of both learners and educators.
Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel
Authors: Lester Sandra N. , Stumpf Megan , Freeman Brandi D. , Mills Lisa , Schiffer Jarad , Semenova Vera , Jia Tao , Desai Rita , Browning Peter , Alston Bailey , Ategbole Muyiwa , Bolcen Shanna , Chen Alexander , David Ebenezer , Manitis Panagiotis , Tatum Heather , Qin Yunlong , Zellner Briana , Drobeniuc Jan , Tejada-Strop Alexandra , Chatterjee Payel , Shrivastava-Ranjan Punya , Jenks M. Harley , McMullan Laura K. , Flint Mike , Spiropoulou Christina F. , Niemeyer Glenn P. , Werner Bonnie J. , Bean Christopher J. , Johnson Jeffrey A. , Hoffmaster Alex R. , Satheshkumar Panayampalli S. , Schuh Amy J. , Owen S. Michele , Thornburg Natalie J.
Published: February 2024

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients’ sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4–96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.
Comparative genomics reveals distinct diversification patterns among LysR-type transcriptional regulators in the ESKAPE pathogen Pseudomonas aeruginosa
Authors: Deery Jamie , Carmody Muireann , Flavin Rhiannon , Tomanek Malwina , O'Keeffe Maria , McGlacken Gerard P. , Reen F. Jerry
Published: February 2024

Pseudomonas aeruginosa, a harmful nosocomial pathogen associated with cystic fibrosis and burn wounds, encodes for a large number of LysR-type transcriptional regulator proteins. To understand how and why LTTR proteins evolved with such frequency and to establish whether any relationships exist within the distribution we set out to identify the patterns underpinning LTTR distribution in P. aeruginosa and to uncover cluster-based relationships within the pangenome. Comparative genomic studies revealed that in the JGI IMG database alone ~86 000 LTTRs are present across the sequenced genomes (n=699). They are widely distributed across the species, with core LTTRs present in >93 % of the genomes and accessory LTTRs present in <7 %. Analysis showed that subsets of core LTTRs can be classified as either variable (typically specific to P. aeruginosa) or conserved (and found to be distributed in other Pseudomonas species). Extending the analysis to the more extensive Pseudomonas database, PA14 rooted analysis confirmed the diversification patterns and revealed PqsR, the receptor for the Pseudomonas quinolone signal (PQS) and 2-heptyl-4-quinolone (HHQ) quorum-sensing signals, to be amongst the most variable in the dataset. Successful complementation of the PAO1 pqsR
- mutant using representative variant pqsR sequences suggests a degree of structural promiscuity within the most variable of LTTRs, several of which play a prominent role in signalling and communication. These findings provide a new insight into the diversification of LTTR proteins within the P. aeruginosa species and suggests a functional significance to the cluster, conservation and distribution patterns identified.
Single Testicular Biopsy: Changes in the vascular architecture of the tunica albuginea
Authors: Oliveira Filho Antonio Barbosa de , Peruquetti Rita Luiza , Rasmussen Lucas Trevizani , Cesar Marcos Teixeira , Cêntola Crescêncio Alberto Pereira , Cedenho Agnaldo Pereira
Published: February 2024

Open testicular biopsy is a commonly indicated procedure for diagnosis of testicular histopathology prior to referral to testicular sperm extraction (TESE) or microsurgical testicular sperm extraction (M-TESE) in men with non-obstructive azoospermia (NOA). There are known hematological changes resulting from the rupture of the blood–testis barrier in the TESE and M-TESE procedures, but changes to the microvasculature have not yet been described when the open biopsy is performed prior to spermatozoid collection for intracytoplasmic sperm injection. In this experimental study, open biopsy was performed on testes from adult rabbits. After a 45 days recovery period, the animals underwent a laparotomy for the surgical removal of the aortic patch, both gonadal arteries, the vasa deferentia, and both testicles. The laparotomy was followed by an angiography. The comparative results demonstrate a breakdown in the vascularization of the testicles biopsied relative to the microvasculature pattern of the tunicae albugineae of the intact testicles. The vascular damage resulting from open testicular biopsy reflects one more negative impact on spermatogenic function of previously lesioned testicles besides the known alterations (fibrosis, decrease in testosterone levels, hematological changes). Therefore, we suggest that the M-TESE should be the choice method for sperm retrieval in men with NOA and it should be planned and performed with simultaneous diagnostic and therapeutic objectives in order to increase the patient’s chances of reproductive success.
Caspase-resistant ROCK1 expression prolongs survival ofEµ-MycB cell lymphoma mice
Authors: Mardilovich Katerina , Naylor Gregory , Julian Linda , Phinichkusolchit Narisa , Keeshan Karen , Blyth Karen , Olson Michael F
Published: February 2024

Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due toEµ-Myctransgene expression.Eµ-Myc; Rock1 NCmice had significantly fewer bone marrow cells relative toEµ-Mycmice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower inEµ-Myc; Rock1 NCmice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death inEµ-Myc; Rock1 NCmice bone marrows being more inflammatory.Rock1 WTrecipient mice transplanted with pre-neoplasticEµ-Myc; Rock1 NCbone marrow cells survived longer than mice transplanted withEµ-Myc; Rock1 WTcells, indicating that the survival benefit was intrinsic to theEµ-Myc; Rock1 NCbone marrow cells. The results suggest that the apoptotic death ofEµ-Myc; Rock1 NCcells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.
The Bacterial Quorum-Sensing Signal 2-Aminoacetophenone Rewires Immune Cell Bioenergetics through the PGC-1α/ERRα Axis to Mediate Tolerance to Infection
Authors: Chakraborty Arijit , Bandyopadhaya Arunava , Singh Vijay K , Kovacic Filip , Cha Sujin , Oldham William M. , Tzika A. Aria , Rahme Laurence G
Published: February 2024

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show thatPseudomonas aeruginosa (PA),a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in macrophages’ mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (MPC1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (ERRα). Consequently, ERRα exhibits weakened binding to the MPC1 promoter. This outcome arises from the impaired interaction between ERRα and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized macrophages. Exogenously added ATP in infected macrophages restores the transcript levels ofMPC1andERR-αandenhances cytokine production and intracellular bacterial clearance. Consistent with thein vitrofindings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association withPApersistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations andPApersistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the PGC-1α/ERRα axis in its influence on MPC1/OXPHOS-dependent energy production andPAclearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.
Experimental evolution in maize with replicated divergent selection identifies plant-height associated SNPs
Authors: Tost Mila , Westhues Cathy , Morrison Ginnie , Kaufmann Dietrich , Beissinger Timothy
Published: February 2024

Experimental evolution studies are common in agricultural research, where they are often deemed “long term selection”. These are often used to perform selection mapping, which involves identifying markers which were putatively under selection based on finding signals of selection left in the genome. A challenge of previous selection mapping studies, especially in agricultural research, has been the specification of robust significance thresholds. This is in large part because long term selection studies in crops have rarely included replication. Usually, significance thresholds in long term selection experiments are based on outliers from an empirical distribution. This approach is prone to missing true positives or including false positives. Under laboratory conditions with model species, replicated selection has been shown to be a powerful tool, especially for the specification of significance thresholds. Another challenge is that commonly used single-marker based statistics may identify neutral linked loci which have hitchhiked along with regions that are actually under selection. In this study, we conducted divergent, replicated selection for short and tall plant-height in a random mating maize population under real field conditions. Selection of the 5% tallest and shortest plants was conducted for three generations. Significance thresholds were specified using the false discovery rate for selection (FDRfS) based on a window-based statistic applied on a statistic leveraging replicated selection (FSTSum). Overall, we found 3 significant regions putatively under selection. One region was located on chromosome 3 close to the plant-height genesDwarf1andiAA8. We applied a haplotype block analysis to further dissect the pattern of selection in significant regions of the genome. We observed patterns of strong selection in the subpopulations selected for short plant height on chromosome 3.
Effective population size does not explain long-term variation in genome size and transposable element content in animals
Authors: Marino Alba , Debaecker Gautier , Fiston-Lavier Anna-Sophie , Haudry Annabelle , Nabholz Benoit
Published: February 2024

Animal genomes exhibit a remarkable variation in size, but the evolutionary forces responsible for such variation are still debated. As the effective population size (Ne) reflects the intensity of genetic drift, it is expected to be a key determinant of the fixation rate of nearly-neutral mutations. Accordingly, the Mutational Hazard Hypothesis postulates lineages with low Neto have bigger genome sizes due to the accumulation of slightly deleterious transposable elements (TEs), and those with high Neto maintain streamlined genomes as a consequence of a more effective selection against TEs. However, the existence of both empirical confirmation and refutation using different methods and different scales precludes its general validation. Using high-quality public data, we estimated genome size, TE content and rate of non-synonymous to synonymous substitutions (dN/dS) as Neproxy for 807 species including vertebrates, molluscs and insects. After collecting available life-history traits, we tested the associations among population size proxies, TE content and genome size, while accounting for phylogenetic non-independence. Our results confirm TEs as major drivers of genome size variation, and endorse life-history traits and dN/dS as reliable proxies for Ne. However, we do not find any evidence for increased drift to result in an accumulation of TEs across animals. Within more closely related clades, only a few isolated and weak associations emerge in fishes and birds. Our results outline a scenario where TE dynamics vary according to lineage-specific patterns, lending no support for genetic drift as the predominant force driving long-term genome size evolution in animals.
Endometriosis Online Communities: A Quantitative Analysis
Authors: Bologna Federica , Thalken Rosamond , Pepin Kristen , Wilkens Matthew
Published: February 2024

Background

Endometriosis is a chronic condition that affects 10% of people with a uterus. Due to the complex social and psychological impacts caused by the condition, people with endometriosis often turn to online health communities (OHCs) for support.

Objective

Prior work identifies a lack of large-scale analyses of endometriosis patient experiences and of OHCs. Our study fills this gap by investigating aspects of the condition and aggregate user needs that emerge from two endometriosis OHCs,r/Endoandr/endometriosis.

Methods

We leverage topic modeling and supervised machine learning to identify associations between a post’s subject matter (“topics”), the people and relationships (“personas”) mentioned, and the type of support the post seeks (“intent”).

Results

The most discussed topics in posts aremedical stories, medical appointments, sharing symptoms, menstruation, andempathy. In addition, when discussingmedical appointments, users are more likely to mention theendometriosis OHCsthanmedical professionals. Furthermore,medical professionalis the least likely of any persona to be associated withempathy. Posts that mentionpartnerorfamilyare likely to discuss topics from thelife issuescategory, in particularfertility. Lastly, we find that while users seek experiential knowledge regarding treatments and healthcare processes, they also wish to vent and to establish emotional connections about the life-altering aspects of the condition.

Conclusions

Endometriosis OHCs provide members a space where they can discuss care pathways, learn to manage symptoms, and receive validation. Our results emphasize the need for greater empathy within clinical settings, easier access to appointments, more information on care pathways, and further support for patient loved ones. In addition, this study demonstrates the value of quantitative analyses of OHCs: they can support and extend findings from small-scale studies about patient experiences and provide insight into hard-to-reach groups. Lastly, analyses of OHCs can help design interventions to improve care, as argued in previous studies.
Associations between Monocyte-to-High Density Lipoprotein Ratio and abdominal aortic calcification: Results of a nationwide survey
Authors: Ran Wei
Published: February 2024

Background

Abdominal aortic calcification (AAC), a critical marker for cardiovascular disease, is strongly correlated with metabolic disorders like diabetes and hypertension. Recent studies have highlighted the Monocyte-to-High Density Lipoprotein Ratio (MHR) as a potential biomarker for assessing the risk of atherosclerosis and cardiovascular diseases.

Methods and Results

This cross-sectional study utilized data from the National Health and Nutrition Examination Surveys (NHANES) 2013-2014, focusing on U.S. adults aged 40 years and above. A total of 3017 participants were included, with AAC evaluated using dual-energy X-ray absorptiometry (DXA) scans, and the severity of AAC quantified based on the Kauppila score system. MHR was investigated for its association with AAC severity, employing multiple linear and multivariable logistic regression models to explore the relationship dynamics. After adjusting for potential confounders, including age, sex, race, socioeconomic factors, and other health-related variables, the analysis revealed a significant association between higher MHR levels and increased AAC scores. Participants with elevated MHR exhibited a greater prevalence and severity of AAC.

Conclusions

The study demonstrates a significant association between elevated MHR and the prevalence and severity of AAC, suggesting the utility of MHR as a predictive biomarker for cardiovascular risk assessment. These findings advocate for the inclusion of MHR in cardiovascular disease management and risk stratification protocols.
A single-cell transcriptomics atlas for the parasitic nematodeHeligmosomoides bakeri: Extrapolating model organism information to non-model systems
Authors: Pollo Stephen M. J. , Liu Hongrui , Coria Aralia Leon , Rosin Nicole , Labit Elodie , Biernaskie Jeff , Finney Constance A. M. , Wasmuth James D.
Published: February 2024

Single-cell atlases aim to collect the gene expression information for every cell type in an organism but can be challenging to perform in non-model organisms. To try to circumvent the problem of having no verified cell type markers in the parasitic nematodeHeligmosomoides bakerito use for an atlas, we attempted to use orthologs of verified markers from the closely related model organismCaenorhabditis elegans. This resulted in a useful comparison between the two worms for each of the cell types recovered in preliminaryH. bakerisingle-cell RNA-sequencing. ForH. bakerimales and females, robustly recovered cell types include the gametes, embryos, and male intestine, while hypodermis, neurons, muscles, and pharyngeal cells were under-represented cell types. The two worms appear to have a similar hypodermis, cuticle, eggshell, and spermatogenesis process. On the other hand, putative cell identities and cell cycle scores suggest the intestine and muscle cells inH. bakerimay still be cycling and dividing, unlike inC. elegans. Additionally, embryogenesis and early development appear to be quite different between the two worms, with only eight out of 94 confirmed paternal contributions to the embryo inC. elegans(with an ortholog) predicted to also be paternal contributions inH. bakeri. Overall, this new dataset allowed me to move beyond the presence or absence of orthologs to include their tissue specificity and expression level similarities and differences when comparing these two worms to better identify biological processes and traits in a parasitic nematode that are modelled well byC. elegans.
Receptor tyrosine kinases CAD96CA and FGFR1 function as the cell membrane receptors of insect juvenile hormone
Authors: Li Yan-Xue , Kang Xin-Le , Li Yan-Li , Wang Xiao-Pei , Yan Qiao , Wang Jin-Xing , Zhao Xiao-Fan
Published: February 2024

Juvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insectHelicoverpa armigera(cotton bollworm), a serious agricultural pest, as a model, we determined that receptor tyrosine kinases (RTKs) cadherin 96ca (CAD96CA) and fibroblast growth factor receptor homologue (FGFR1) function as JH cell membrane receptors by their roles in JH-regulated gene expression, larval status maintaining, rapid intracellular calcium increase, phosphorylation of JH intracellular receptor MET1 and cofactor Taiman, and high affinity to JH III. Gene knockout ofCad96caandFgfr1by CRISPR/Cas9 in embryo and knockdown in various insect cells, and overexpression of CAD96CA and FGFR1 in mammalian HEK-293T cells all supported CAD96CA and FGFR1 transmitting JH signal as JH cell membrane receptors.
Decreases in liver cT1 accurately reflect histological improvement induced by therapies in MASH: a multi-centre pooled cohort analysis
Authors: Alkhouri Naim , Beyer Cayden , Shumbayawonda Elizabeth , Andersson Anneli , Yale Kitty , Rolph Timothy , Chung Raymund , Vuppalanchi Raj K , Cusi Kenneth , Loomba Rohit , Dennis Andrea , Pansini Michele
Published: February 2024

Background & Aims

Iron corrected T1 (cT1) is an MRI derived biomarker of liver disease activity. Emerging data suggest a change in cT1 of ≥ 80 ms reflects histological improvement. We aimed to validate the association between the ≥ 80 ms decline in cT1 and histological improvement, specifically the resolution of MASH.

Methods

A retrospective analysis of study participants from three interventional clinical trials with histologically confirmed MASH (n = 150) who underwent multi-parametric MRI to measure cT1 (LiverMultiScan®) and biopsies at baseline and end of study. Histological responders were defined using the four criteria: (1) a decrease in NAFLD Activity score (NAS) ≥ 2 with no worsening in fibrosis, (2) a decrease in fibrosis ≥ 1 stage with no worsening in NAS, (3) both a NAS decrease ≥ 2 and a fibrosis decrease ≥ 1, and (4) MASH resolution with no worsening in fibrosis. Difference in the magnitude of change in cT1 between responders and non-responders was assessed.

Results

Significant decreases in cT1 were observed in responders for all the histological criteria. The largest decrease was observed for those achieving MASH resolution, and was 119ms, compared to 43ms for non-responders. The optimal reduction in cT1 for separating responders from non-responders for MASH resolution was −74ms (64ms-73ms for the other criteria), in close agreement with the previously predefined threshold of −80ms. Those achieving an ≥ 80 ms reduction in cT1 were substantially more likely to achieve histological response with odds ratios ranging from 2.7 to 6.3.

Conclusions

These results demonstrate that a reduction in cT1 of 80 ms was associated with histological response supporting the utility of cT1 to predict clinical improvement in patients undergoing therapeutic intervention.
Neutrophil-to-Lymphocyte Ratio as a Prognostic Indicator in COVID-19: Evidence from a Northern Tanzanian Cohort
Authors: Kyala Norman J. , Mboya Innocent B. , Shao Elichilia , Sakita Francis M. , Kilonzo Kajiru G. , Shirima Laura J , Sadiq Abid M. , Mkwizu Elifuraha , Chamba Nyasatu , Marandu Annette , Muhali Sophia , Raza Faryal M , Ndale Eliasa , Bayo Damasi F. , Mujuni Daniel P. , Lyamuya Furaha
Published: February 2024

Background

COVID-19 caused a profound global impact, resulting in significant cases and deaths. The progression of COVID-19 clinical manifestations is influenced by a dysregulated inflammatory response. Early identification of the subclinical progression is crucial for timely intervention and improved patient outcomes. While there are various biomarkers to predict disease severity and outcomes, their accessibility and affordability pose challenges in resource-limited settings. We explored the potentiality of the neutrophil-to-lymphocyte ratio (NLR) as a cost-effective inflammatory marker to predict disease severity, clinical deterioration, and mortality in affected patients.

Methodology

A hospital-based retrospective cohort study was conducted at KCMC Hospital among COVID-19 patients followed from admission to discharge between 1stMarch 2020 and 31stMarch 2022. NLR was calculated as the absolute neutrophil count in µL divided by the absolute lymphocyte count in µL. The NLR cut-off value was determined using Receiver Operating Characteristic (ROC) analysis and assessed its predictive ability at admission for in-hospital mortality. The Chi-square test compared the proportion of NLR by patient characteristics. The association of NLR with disease severity and mortality was analyzed using the modified Poisson and Cox regression models, respectively.

Results

The study included 504 patients, with a median age of 64 years, 57.1% were males, and 68.3% had severe COVID-19. The in-hospital COVID-19 mortality rate was 37.7%. An NLR cutoff value of 6.1 or higher had a sensitivity of 92.1% (95% CI 89.2%–94.0%) and a specificity of 92.0% (95% CI 89.7%–94.4%). Additionally, 39.5% of patients with an NLR value of 6.1 or higher had increased risk of severe disease, subsequent clinical deterioration, and mortality.

Conclusion and recommendation

An NLR value of 6.1 or higher at the time of hospital admission associated with severe disease, clinical deterioration, and mortality in patients with COVID-19. Integration of NLR as a prognostic parameter in COVID-19 prognosis scales could improve risk assessment and guide appropriate management strategies for COVID-19 patients, as well as for potential future viral-related pneumonias. Further prospective studies are necessary to validate these findings and evaluate the clinical utility of NLR in larger cohorts of patients.
Designed mosaic nanoparticles enhance cross-reactive immune responses in mice
Authors: Wang Eric , Cohen Alexander A. , Caldera Luis F. , Keeffe Jennifer R. , Rorick Annie V. , Aida Yusuf M. , Gnanapragasam Priyanthi N.P. , Bjorkman Pamela J. , Chakraborty Arup K.
Published: February 2024

Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naïve and COVID-19 pre-vaccinated mice revealed that mosaic-7COMelicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COMtargeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COMelicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COMelicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COMto protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.
Gender and leadership evaluations: what happens if we actually measure expectations–behavior incongruence?
Authors: Eichenauer Connor , Ryan Ann Marie
Published: February 2024

Purpose

Role congruity theory and gender stereotypes research suggests men are expected to engage in agentic behavior and women in communal behavior as leaders, and that role violation results in backlash. However, extant gender and leadership research does not directly measure expectations–behavior incongruence. Further, researchers have only considered one condition of role incongruence – display of counter-role behavior – and have not considered the outcomes of failing to exhibit role-congruent behavior. Additionally, few studies have examined outcomes for male leaders who violate gender role prescriptions. The present study aims to address these shortcomings by conducting a novel empirical test of role congruity theory.

Design/Methodology/approach

This experimental study used polynomial regression to assess how followers evaluated leaders under conditions of incongruence between follower expectations for men and women leaders’ behavior and leaders’ actual behavior (i.e. exceeded and unmet expectations). Respondents read a fictional scenario describing a new male or female supervisor, rated their expectations for the leader’s agentic and communal behavior, read manipulated vignettes describing the leader’s subsequent behavior, rated their perceptions of these behaviors, and evaluated the leader.

Findings

Followers expected higher levels of communal behavior from the female than the male supervisor, but no differences were found in expectations for agentic behavior. Regardless of whether expectations were exceeded or unmet, supervisor gender did not moderate the effects of agentic or communal behavior expectations–perceptions incongruence on leader evaluations in polynomial regression analyses (i.e. male and female supervisors were not evaluated differently when displaying counter-role behavior or failing to display role-congruent behavior).

Originality/value

In addition to providing a novel, direct test of role congruity theory, the study highlighted a double standard in gender role-congruent behavior expectations of men and women leaders. Results failed to support role congruity theory, which has implications for the future of theory in this domain.
A multi-method case study of a police agency’s response to the COVID-19 pandemic
Authors: Lum Cynthia , Koper Christopher S. , Goodier Michael , Johnson William , Krause James
Published: February 2024

Purpose

We present the results of one of the only in-depth studies of a police agency’s internal and external response to the coronavirus pandemic of 2020 (COVID-19). This study emphasizes the importance of law enforcement agencies conducting comprehensive case studies and after-action assessments to prepare, prevent and respond to prolonged public health crises and showcases the profound (and lingering) effects of COVID-19 on police organizations.

Design/methodology/approach

This multi-method case study combines document analysis, a workforce survey, a community survey, interviews and analysis of administrative data to detail and assess the agency’s internal and operational responses to the pandemic and the reactions of employees and community members to those responses.

Findings

Despite agency strategies to mitigate the pandemic’s effects, employees cited very high stress levels one year after the pandemic and a third of sworn officers considered leaving the policing profession altogether during the first two years of the COVID-19 pandemic. Several policies intended by the agency to protect employee health and maintain staffing needs kept workforce levels steady but may have increased feelings of organizational injustice in both sworn and non-sworn individuals, with variation across racial and gender groups. A jurisdiction-wide community survey indicated general support for the police department’s responses but a preference for in-person rather than telephone-based responses to service calls. Officers, however, preferred continuing remote responses even after the pandemic subsided.

Originality/value

To the best of our knowledge, this is one of the only in-depth case studies that examine a police agency’s internal and external responses to COVID-19 and the sworn, non-sworn and community reactions to those responses.
Perceived customer value and willingness to pay: strategies for improving and sustaining water service quality
Authors: Murrar Abdullah , Paz Veronica , Batra Madan , Yerger David
Published: February 2024

Purpose

Several studies have examined the relationship between service quality and willingness to pay in many industries. However, this relationship has not been explored through the lens of customer perceived value and their willingness to pay for improving and sustaining water service. This study aims to examine the impact of technical and functional service quality dimensions on customer perceived value and assess the influence of customer perceived value and socio-economic factors on customers' willingness to pay for improving and sustaining the water service.

Design/methodology/approach

Technical service quality includes core water service such as water delivery and maintenance, while functional service quality refers to the appearance of facilities, employees’ dress, and communication. SERVQUAL questionnaire responses were collected from 333 Palestinian household customers. Cronbach’s alpha was conducted to measure internal consistency and convergent validity. Path analysis was utilized to evaluate a causal diagram by examining the relationships among the constructs.

Findings

The results showed that technical and functional service quality and relative price explain 52% of the customer perceived value variation. Additionally, the results revealed that customer perceived value, technical service quality, and relative price significantly impact the customer’s willingness to pay for improving and sustaining service. In contrast, the functional service quality and socio-economic factors have insignificant effects. These predictors explain 60% of the customer’s willingness to pay for improving and sustaining service.

Practical implications

The study suggests that water providers should prioritize improving and sustaining technical service quality to increase customer willingness to pay. Furthermore, they should be aware that other factors, such as employee appearance and politeness, are less influential in driving customers’ willingness to pay.

Originality/value

The study presents a water service improvement model that utilizes data from a developing country to assess the influence of perceived customer value, along with its dimensions, on the willingness to pay for improving and sustaining water service quality.
Clinical features of patients with connective tissue disease with anti–human upstream binding factor antibodies: A single‐center retrospective study
Authors: Fushida Natsumi , Horii Motoki , Fujii Ko , Mizumaki Kie , Kitano Tasuku , Sawada Kaori , Numata Natsuki , Oishi Kyosuke , Maeda Shintaro , Hamaguchi Yasuhito , Watanabe Satoshi , Matsushita Takashi
Published: February 2024

Anti–human upstream‐binding factor (anti‐hUBF) antibodies have been reported predominantly in patients with connective tissue diseases (CTDs); these have also been reported in patients without CTDs such as hepatocellular carcinoma. Because of the low frequency of expression and few case reports, there is no consensus on the clinical significance of these antibodies. Thus, we aimed to examine the clinical features of patients with anti–hUBF antibodies and analyzed 1042 patients with clinically suspected CTDs. The presence of anti–hUBF antibodies was screened using immunoprecipitation assays. Of the 1042 patients, 19 (1.82%) tested positive for anti–hUBF antibodies; among them, 10 (56%) were diagnosed with undifferentiated CTD (UCTD), six with systemic sclerosis (SSc) and three with other diseases. Five of the 10 patients with UCTD were referred to our hospital with suspected SSc. None of the five patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria, but three scored seven points, a relatively high score. Six anti–hUBF‐positive patients with SSc had a significantly lower modified Rodnan skin score (mRSS) than that of anti–hUBF‐negative patients with SSc (2 [0–2] vs 7 [0–49], p < 0.01). Compared with anti–topoisomerase I‐positive patients, anti–hUBF‐positive patients had a significantly lower mRSS (2 [0–2] vs 13 [0–42], p < 0.01) and lower incidence of scleroderma renal crisis (0 of 6 vs 8 of 184, p < 0.01). Compared with anti–centromere‐positive patients, anti–hUBF‐positive patients had a higher incidence of interstitial lung disease (ILD), but the difference was not statistically significant (4 of 6 vs 19 of 239). In conclusion, anti–hUBF antibodies were predominantly detected in patients with CTDs and UCTD. In patients with CTDs, SSc exhibited a high ratio, displaying a lower mRSS and higher incidence of ILD. In patients with UCTD, careful follow‐up is recommended as they may develop CTDs in the future.
Annual recurrence of prokaryotic climax communities in shallow waters of the North Mediterranean
Authors: Celussi Mauro , Manna Vincenzo , Banchi Elisa , Fonti Viviana , Bazzaro Matteo , Flander‐Putrle Vesna , Klun Katja , Kralj Martina , Orel Neža , Tinta Tinkara
Published: February 2024

In temperate coastal environments, wide fluctuations of biotic and abiotic factors drive microbiome dynamics. To link recurrent ecological patterns with planktonic microbial communities, we analysed a monthly‐sampled 3‐year time series of 16S rRNA amplicon sequencing data, alongside environmental variables, collected at two stations in the northern Adriatic Sea. Time series multivariate analyses allowed us to identify three stable, mature communities (climaxes), whose recurrence was mainly driven by changes in photoperiod and temperature. Mixotrophs (e.g., Ca. Nitrosopumilus, SUP05 clade, and Marine Group II) thrived under oligotrophic, low‐light conditions, whereas copiotrophs (e.g., NS4 and NS5 clades) bloomed at higher temperatures and substrate availability. The early spring climax was characterised by a more diverse set of amplicon sequence variants, including copiotrophs associated with phytoplankton‐derived organic matter degradation, and photo‐auto/heterotrophic organisms (e.g., Synechococcus sp., Roseobacter clade), whose rhythmicity was linked to photoperiod lengthening. Through the identification of recurrent climax assemblages, we begin to delineate a typology of ecosystem based on microbiome composition and functionality, allowing for the intercomparison of microbial assemblages among different biomes, a still underachieved goal in the omics era.
Using benefit transfer to estimate housing value increases from improved water clarity: A case study of lakes in Kosciusko County, Indiana
Authors: Burlingame Matthew , Guignet Dennis , Heberling Matthew T. , Papenfus Michael
Published: February 2024

This study provides step‐by‐step guidance for practitioners and local stakeholders on how to use existing study results to conduct benefit transfer (BT), and ultimately make informed predictions of how improvements in lake water clarity may benefit surrounding communities. The procedures are demonstrated using a publicly available meta‐dataset developed by the United States Environmental Protection Agency, and a subsequent meta‐analysis that synthesizes the literature on how improvements in water clarity impact home values. The BT procedures are demonstrated using a case study of 14 large lakes in Kosciusko County, Indiana. Lake‐specific average increases in home values, as well as the value of the housing stock in aggregate, are calculated for illustrative improvements in lake water clarity. This analysis provides a critical bridge to better connect high‐quality, academic research with real‐world policy analysis, and ultimately serves to better equip local governments and stakeholders to make more informed policy and land use decisions.
Widespread analytical pitfalls in empirical coexistence studies and a checklist for improving their statistical robustness
Authors: Terry J. Christopher D. , Armitage David W.
Published: February 2024

Modern coexistence theory (MCT) offers a conceptually straightforward approach for connecting empirical observations with an elegant theoretical framework, gaining popularity rapidly over the past decade. However, beneath this surface‐level simplicity lie various assumptions and subjective choices made during data analysis. These can lead researchers to draw qualitatively different conclusions from the same set of experiments. As the predictions of MCT studies are often treated as outcomes, and many readers and reviewers may not be familiar with the framework's assumptions, there is a particular risk of ‘researcher degrees of freedom’ inflating the confidence in results, thereby affecting reproducibility and predictive power.

To tackle these concerns, we introduce a checklist consisting of statistical best practices to promote more robust empirical applications of MCT. Our recommendations are organised into four categories: presentation and sharing of raw data, testing model assumptions and fits, managing uncertainty associated with model coefficients and incorporating this uncertainty into coexistence predictions.

We surveyed empirical MCT studies published over the past 15 years and discovered a high degree of variation in the level of statistical rigour and adherence to best practices. We present case studies to illustrate the dependence of results on seemingly innocuous choices among competition model structure and error distributions, which in some cases reversed the predicted coexistence outcomes. These results demonstrate how different analytical approaches can profoundly alter the interpretation of experimental results, underscoring the importance of carefully considering and thoroughly justifying each step taken in the analysis pathway.

Our checklist serves as a resource for authors and reviewers alike, providing guidance to strengthen the empirical foundation of empirical coexistence analyses. As the field of empirical MCT shifts from a descriptive, trailblazing phase to a stage of consolidation, we emphasise the need for caution when building upon the findings of earlier studies. To ensure that progress made in the field of ecological coexistence is based on robust and reliable evidence, it is crucial to subject our predictions, conclusions and generalisability to a more rigorous assessment than is currently the trend.
Cases with the H syndrome presenting with skin and bone findings
Authors: Kose Hulya , Baskaya Merve Deniz , Kilic Sara Sebnem
Published: February 2024

Background

The H syndrome is an autosomal recessive disease characterized by hyperpigmentation, hypertrichosis and sensorineural hearing loss.

Methods

A mutation in the coding of the human equilibrative nucleoside transporter 3 (hENT3) within the SLC29A3 gene on chromosome 10q22 leads to the manifestation of this disease. In this report, we present two cases of H syndrome.

Results

The first patient exhibits hyperpigmentation, hypogonadism, Type 1 diabetes mellitus, arthritis and osteoporosis. The second patient experiences hyperpigmentation, hypertrichosis, osteopenia and hypogonadism.

Conclusion

Our objective is to broaden the clinical spectrum of H syndrome, highlighting the involvement of arthritis, hyperinflammation and low bone mineral density in individuals with this disorder.
Long‐term outcomes of children after prenatal exposure to maternal cancer and its treatment
Authors: Huis in ’t Veld Evangeline A. , Van Assche Indra A. , Amant Frederic
Published: February 2024

The incidence of antenatal cancer is increasing, prompting a medical‐ethical evaluation. The International Network on Cancer, Infertility, and Pregnancy (INCIP) was established to study cancer treatment safety during pregnancy and its impact on maternal and child health. Pivotal research has led to a paradigm shift in clinical management, demonstrating the feasibility and safety of most antenatal oncological treatments. Short‐term outcomes reveal normal growth and cardiac function in the exposed offspring, but caution is advised against first‐trimester chemotherapy. Psychological impact studies highlight the elevated levels of distress in pregnant cancer patients, underscoring the need for personalized information and ongoing psychological support. Long‐term follow‐up studies address gaps in postnatal impacts, while research into specific chemotherapeutic agents continues. Despite generally reassuring outcomes, continued monitoring is crucial, especially in families, such as those where the child was born premature after cancer (treatment) during pregnancy or where mothers are frequently absent due to continued illness or have died from. The ongoing INCIP child follow‐up initiative aims to further elucidate knowledge gaps, emphasizing the importance of large‐scale studies and personalized patient care.