bluuebunny/crossref_metadata_2025 huggingface dataset:
Barn Swallows in East Asia show strong tolerance against nest mites
Authors: Liu Yu , Tian Li , Zhou Zhuoya , Gao Kai , Chen De , Li Donglai , Wang Yong , Zhang Zhengwang
Published: January 2023

Hosts defend against parasites through two main strategies: resistance and tolerance. These two strategies have different influences on the parasite load of the host and so have variable effects on the fitness of parasites. In this study, we investigated the strategy used by the Barn Swallow (Hirundo rustica) to defend against a hematophagous mite (Dermanyssus hirundinis) in East Asia. For the first time, we found Barn Swallows were parasitized by D. hirundinis in Asia and, in northeastern China, over 60% of broods were parasitized. We examined whether swallows with better body condition or the males with more extravagant sexually selected traits (longer tail streamers or redder ventral plumage) showed stronger resistance or tolerance to these parasites. The results showed that males with more extravagant sexual ornaments had weaker resistance (heavier brood mite load) than males with less extravagant traits; however, the heavier mite load was likely to be a byproduct of larger brood size. Moreover, the Barn Swallow population showed strong tolerance against the parasite (i.e. the brood mite load did not affect brood size or nestling body mass). It is worth noting that male swallows with redder breast plumage showed weaker tolerance (lower seasonal reproductive success) than other males. Further, we conducted experimental ectoparasite manipulations in 46 Barn Swallow nests to verify the potential effect of these parasites on the body condition of nestlings. Neither the body mass nor the hemoglobin concentration differed between the designed groups; however, the hemoglobin concentration of nestlings decreased with mite load. We concluded that the Barn Swallow population in East Asia used the tolerance strategy, rather than resistance to defend against nest mites, and the ectoparasitic mite did not appear to be a strong selective factor for reproductive success owing to the strong tolerance of the studied Barn Swallow population.
A new solution for the deformations of an initially elliptical elastic-walled tube
Authors: Netherwood D J , Whittaker R J
Published: January 2023

We investigate the small-amplitude deformations of a long thin-walled elastic tube having an initially axially uniform elliptical cross-section. The tube is deformed by a (possibly non-uniform) transmural pressure. At leading order, its deformations are shown to be governed by a single partial differential equation (PDE) for the azimuthal displacement as a function of the axial and azimuthal co-ordinates and time. Previous authors have obtained solutions to this PDE by making ad hoc approximations based on truncating an approximate Fourier representation. In this article, we instead write the azimuthal displacement as a sum over the azimuthal eigenfunctions of a generalised eigenvalue problem and show that we are able to derive an uncoupled system of linear PDEs with constant coefficients for the amplitude of the azimuthal modes as a function of the axial co-ordinate and time. This results in a formal solution of the whole system being found as a sum over the azimuthal modes. We show that the $n$th mode’s contribution to the tube’s relative area change is governed by a simplified second-order PDE and examine the case in which the tube’s deformations are driven by a uniform transmural pressure. The relative errors induced by truncating the series solution after the first and second terms are then evaluated as a function of both the ellipticity and pre-stress of the tube. After comparing our results with Whittaker et al. (A rational derivation of a tube law from shell theory, Q. J. Mech. Appl. Math. 63 (2010) 465–496), we find that this new method leads to a significant simplification when calculating contributions from the higher-order azimuthal modes, which in turn makes a more accurate solution easier to obtain.
Air pollution and respiratory infections: the past, present, and future
Authors: Monoson Alexys , Schott Evangeline , Ard Kerry , Kilburg-Basnyat Brita , Tighe Robert M , Pannu Sonal , Gowdy Kymberly M
Published: January 2023

Air pollution levels across the globe continue to rise despite government regulations. The increase in global air pollution levels drives detrimental human health effects, including 7 million premature deaths every year. Many of these deaths are attributable to increased incidence of respiratory infections. Considering the COVID-19 pandemic, an unprecedented public health crisis that has claimed the lives of over 6.5 million people globally, respiratory infections as a driver of human mortality is a pressing concern. Therefore, it is more important than ever to understand the relationship between air pollution and respiratory infections so that public health measures can be implemented to ameliorate further morbidity and mortality. This article aims to review the current epidemiologic and basic science research on interactions between air pollution exposure and respiratory infections. The first section will present epidemiologic studies organized by pathogen, followed by a review of basic science research investigating the mechanisms of infection, and then conclude with a discussion of areas that require future investigation.
COVID-19 vaccine equity in Africa
Authors: Turyasingura Natasha , James Wilmot G , Vermund Sten H
Published: January 2023

The coronavirus disease 2019 (COVID-19) pandemic has dominated global health discourse since early 2020. By early 2021, the unprecedented speed of vaccine development against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by government, academia and industry contributed biotechnological tools to reduce severe COVID-19 infections, hospitalizations and deaths. However, vaccine distribution has not been equitable. We address one element of this challenge, namely the low COVID-19 vaccination rates in African countries, which lag behind higher-income nations. We evaluate key obstacles to initiatives addressing this inequity and emphasize Africa-based research and development as a sustainable solution to ensuring vaccine equity in Africa.
Viromes of Field-Grown Tomatoes and Peppers in Tennessee Revealed by RNA Sequencing Followed by Bioinformatic Analysis
Authors: Dias Naymã P. , Hu Rongbin , Hale Frank A. , Hansen Zachariah R. , Wszelaki Annette , Domier Leslie L. , Hajimorad M. R.
Published: January 2023

The prevalent viruses in a population of 106 tomato and 53 pepper field-grown plants in Tennessee was investigated by RNA sequencing and analysis as two separate pools of ribosomal-depleted total RNA. Contigs of potato leafroll virus (PLRV), red clover vein mosaic virus, tomato spotted wilt virus, and a novel rhabdovirus were detected only in tomato and those of bell pepper endornavirus (BPEV) and pepper cryptic virus 2 (PCV-2) only in pepper. Additionally, contigs of five other viruses (solanum nigrum ilarvirus 1, SNIV-1; southern tomato virus, STV; tobacco vein-clearing virus, ToVCV; tomato mosaic virus, ToMV; and tomato ringspot virus, ToRSV) were detected in both tomatoes and peppers. Moreover, contigs were assembled of a potentially novel tobamovirus from both tomatoes and peppers. The presence of PLRV, STV, ToVCV, and the novel tobamovirus sequences in the original tomato samples and those of BPEV, PCV-2, ToMV, and ToRSV in the original pepper samples were confirmed by RT-PCR followed by Sanger sequencing. This study represents the first survey of viromes of field-grown tomatoes and peppers in Tennessee. To the best of our knowledge, SNIV-1, STV, and ToVCV have not been reported previously to be associated with peppers elsewhere in the world.
PA and NP onboarding in primary care
Authors: Ortiz Pate Nathalie , Barnes Hilary , Batchelder Heather R. , Anglin Lorraine , Sanchez Mara , Everett Christine , Morgan Perri
Published: January 2023

Objective:

To describe new graduate physician associate/assistant (PA) and NP perspectives of onboarding programs in their first primary care position.

Methods:

Thirteen semistructured interviews were conducted with new graduate PAs and NPs who participated in onboarding programs. Interviews were transcribed and then analyzed using an inductive coding methodology.

Results:

Analyses revealed nine thematic concepts that are described in two frameworks. Structural components are improving competence, training on the electronic health record (EHR), promoting mentorship, orienting to organizational dynamics, tailoring ramp-up of patient scheduling, clarifying expectations, and providing clear organizational support. Psychosocial factors are creating comfort and building self-confidence.

Discussion:

The results describe and delineate important components for onboarding that administrators can incorporate into existing and future programs.

Conclusion:

Understanding participants' experiences with onboarding programs is essential for ensuring successful transition to practice for new graduate PAs and NPs.
Prospective Comparison Between Manual and Computer-Assisted (FOX) Cochlear Implant Fitting in Newly Implanted Patients
Authors: Wathour Justine , Govaerts Paul J. , Derue Lucie , Vanderbemden Suzanne , Huaux Hélène , Lacroix Emilie , Deggouj Naïma
Published: January 2023

Objective:

A prospective, longitudinal, randomized controlled trial with an original crossover design for 1 year was conducted to compare manual fitting to artificial intelligence-based fitting in newly implanted patients.

Design:

Twenty-four patients who received their first cochlear implant (CI) were randomly assigned to the manual or Fitting to Outcome eXpert (FOX) arm; they followed the corresponding fitting procedures for 1 year. After 1 year, each patient was switched to another arm. The number of fittings, auditory outcomes (pure-tone thresholds, loudness scaling curves, spectral discrimination scores, bisyllabic word recognition in quiet and noise, and speech tracking), fitting session questionnaire, and CI parameters (T level, C level, Threshold Sound Pressure Level (T-SPL), Comfortable Sound Pressure Level (C-SPL), and loudness growth value) were compared between the two groups. Differences between the two groups were analyzed using the Mann-Whitney test, and Holm corrections were applied for multiple statistical tests. At the end of the crossover session, patients were offered the choice to continue with their old or new map.

Results:

As early as 3 mo postactivation, the FOX group showed less variability and significantly better speech intelligibility in quiet conditions at 40 and 55 dB SPL and noise (p < 0.05) with median phoneme scores of 50%, 70%, and 50% at 55, 70, and 85 dB SPL compared with 45%, 50%, and 40%, respectively. This group showed better results at 12 mo postactivation (p < 0.05). In the manual group, 100% of the patients decided to keep the new FOX map, and 82% performed better with the FOX map. In the FOX group, 63% of the patients decided to keep the manual map, although the measurable outcome had not improved. In this group, participants reported to prefer the manual map because it felt more comfortable, even if the FOX map gave better measured outcome.

Conclusion:

Although the study size remains relatively small, the AI-FOX approach was equivalent to or even outperformed the manual approach in hearing performance, comfort, and resources. Furthermore, FOX is a tool capable of continuous improvement by comparing its predictions with observed results and is continuously learning from clinicians’ practice, which is why this technology promises major advances in the future.
CDKN2B-AS1 is overexpressed in polycystic ovary syndrome and sponges miR-181a to promote granulosa cell proliferation
Authors: Huang Yan , Zhang Yuying , Zhou Yuzhen , Chen Ying , Zhu Qianmeng
Published: January 2023

MiR-181a suppresses the proliferation of mouse granulosa cells, which participate in polycystic ovary syndrome (PCOS), suggesting the potential role of miR-181a in PCOS. Our bioinformatics analysis revealed that miR-181a could bind CDKN2B-AS1, a lncRNA regulates ovarian endometriosis. This research was, therefore, conducted to explore the potential crosstalk between CDKN2B-AS1 and miR-181a in PCOS. Expression analysis of CDKN2B-AS1 and miR-181a in follicular fluid from 60 PCOS patients and 60 controls was done with reverse transcriptions-quantitative PCRs. The direct interaction between CDKN2B-AS1 and miR-181a was predicted by IntaRNA and confirmed by RNA pull-down assay. CDKN2B-AS1 in nuclear and cytoplasm of granulosa cells was detected by cellular fractionation assay. The role of CDKN2B-AS1 and miR-181a in granulosa cell proliferation was analyzed by 5-bromodeoxyuridinc assay. In this study, CDKN2B-AS1 was expressed in high amounts in PCOS, whereas miR-181a was downregulated in PCOS, CDKN2B-AS1 was detected in both nucleus and cytoplasm. Although CDKN2B-AS1 and miR-181a were not closely correlated, CDKN2B-AS1 directly interacted with miR-181a. CDKN2B-AS1 and miR-181a overexpression failed to affect the expression of each other. In addition, the inhibitory effect of miR-181a on granulosa cell proliferation was attenuated by CDKN2B-AS1. CDKN2B-AS1 is overexpressed in PCOS and may sponge miR-181a to promote granulosa cell proliferation. Our study characterized a novel CDKN2B-AS1/miR-181a pathway in PCOS. This novel pathway may serve as a potential target to treat PCOS.
Epithelial ingrowth after SMILE
Authors: Ding Xuan , Fu Dan , Wang Lin , Zhou Xingtao , Yu Zhiqiang
Published: January 2023

Epithelial ingrowth is a rarely reported complication after small-incision lenticule extraction (SMILE). The case of a 41-year-old man with epithelial ingrowth in his left eye 20 days after SMILE is presented. He presented to the refractive center for a routine follow-up visit without any complaint, but the left eye revealed a small strip of corneal opacity. A corneal foreign body was removed and was verified as a corneal epithelium block after the pathology examination. Follow-up examinations showed good results.
Acute corneal hydrops with iatrogenic keratoconus 20 years after radial keratotomy
Authors: Gill Hannah , Shew William , McGhee Charles , Crawford Alexandra
Published: January 2023

A 51-year-old man presented with a history of cloudy vision in the left eye with minimal discomfort. On slitlamp examination, he had 4 well-healed radial keratotomy (RK) incisions in each eye. Severe corneal edema was observed in the inferotemporal aspect of the left eye, consistent with acute hydrops. The patient was managed conservatively with observation and frequent topical lubrication for comfort. The clinical signs of corneal edema resolved over a period of several months, with worsened resultant scarring around the 5-o'clock keratotomy incision. Corneal ectasia is an established late complication of RK. Of interest in this case, the area of corneal hydrops was well demarcated because the RK scars formed a barrier against further progression of corneal edema.
Investigation of the forkhead box protein P2 gene by the next-generation sequence analysis method in children diagnosed with specific learning disorder
Authors: Yazıcı Merve , Yektaş Çiğdem , Eröz Recep , Kaplan Karakaya Elif Sümeyra , Sarıgedik Enes
Published: January 2023

Objective

It was aimed to investigate the role of the forkhead box protein P2 (FOXP2) gene in the cause of specific learning disorder (SLD) with the next-generation sequencing method.

Material and methods

The study included 52 children diagnosed with SLD and 46 children as control between the ages of 6–12 years. Interview Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifelong Version in Turkish, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-Based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders, Specific Learning Disability Test Battery were applied to all participants. The FOXP2 gene was screened by the next-generation sequencing (NGS) method in all participants.

Results

A total of 17 variations were detected in the FOXP2 gene in participants. The number and diversity of variations were higher in the patient group. In the patient group, c.1914 + 8A>T heterozygous variation and three different types of heterozygous variation (13insT, 13delT and 4dup) in the c.1770 region were detected. It was found that the detected variations showed significant relationships with the reading phenotypes determined by the test battery.

Conclusion

It was found that FOXP2 variations were seen more frequently in the patient group. Some of the detected variations might be related to the clinical phenotype of SLD and variations found in previous studies from different countries were not seen in Turkish population. Our study is the first to evaluate the role of FOXP2 gene variations in children with SLD in Turkish population, and novel variations in the related gene were detected.
Psychosis and autism without functional regression in a patient with Kleefstra syndrome
Authors: Colijn Mark A. , Lakusta Cherelyn M. , Marcadier Julien L.
Published: January 2023

Kleefstra syndrome is a rare genetic disorder caused by haploinsufficiency of the euchromatic histone lysine methyltransferase 1 (EHMT1) gene. It is characterized by a variety of dysmorphic features, comorbid medical issues, and developmental delays/intellectual disability. Neuropsychiatric symptoms may also occur, including autistic features and psychosis, and are often accompanied by functional regression. However, the phenomenology of psychotic symptoms in this syndrome has not been well described in the literature. As such, in this brief report, we review the literature with respect to the occurrence of psychosis in Kleefstra syndrome and describe the symptom profile of a 35-year-old affected male with an intellectual disability, autism spectrum disorder, and schizophrenia (in association with manic features). This is the first report of psychotic symptoms fully remitting in response to zuclopenthixol therapy in an individual with Kleefstra syndrome. This case is also unique as it demonstrates that functional regression does not necessarily coincide with the development of schizophrenia-like presentations in affected individuals.
Genetics of nonpharmacological treatments of depression
Authors: Zanardi Raffaella , Carminati Matteo , Attanasio Francesco , Fabbri Chiara , Serretti Alessandro
Published: January 2023

Nonpharmacological antidepressant treatments are effective and well tolerated in selected patients. However, response is heterogeneous and validated biomarkers would be precious to aid treatment choice. We searched Pubmed, Scopus, and Google Scholar until May 2022 for original articles evaluating the association of genetic variables with the efficacy of nonpharmacological treatments for major depressive episodes. Most studies analyzed small sample sizes using the candidate gene approach, leading to poorly replicated findings that need to be interpreted cautiously. The few available methylome-wide and genome-wide association studies (GWASs) considered only electroconvulsive therapy (ECT) and cognitive-behavioral therapy in small samples, providing interesting findings by using polygenic risk scores. A deeper knowledge of the genetic factors implicated in treatment response may lead to a better understanding of the neurobiological mechanisms of nonpharmacological therapies for depression, and depression itself. Future GWAS are going to expand their sample size, thanks to consortia such as the gen-ECT-ic consortium.
Light Scattering Technology and MALDI-TOF MS in the microbiological fast-track of bloodstream infections: potential impact on antimicrobial treatment choices in a real-life setting
Authors: Curtoni Antonio , Ghibaudo Davide , Veglio Caterina , Imperatore Luigi , Bianco Gabriele , Castiglione Anna , Ciccone Giovannino , Scaglione Luca , Scabini Silvia , Corcione Silvia , De Rosa Francesco Giuseppe , Costa Cristina , Cavallo Rossana
Published: January 2023

Introduction. Rapid identification (ID) and antimicrobial susceptibility testing (AST) of bloodstream infections (BSI) pathogens are fundamental to switch from empirical to targeted antibiotic therapy improving patients outcome and reducing antimicrobial resistance spreading.

Hypothesis. The adoption of a rapid microbiological protocol (RP) based on Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS) and Light Scattering Technology (LST) for rapid diagnosis of BSI could positively impact on patients' antimicrobial management.

Aim. The study aim was to evaluate a RP for BSI microbiological diagnosis in terms of accuracy, turnaround time (TAT) and potential therapeutic impact.

Methodology. A prospective observational study was conducted: monomicrobial bacterial blood cultures of septic patients were analysed in parallel by RP and standard protocol (SP). In RP the combination of MALDI-TOF MS and LST was used for rapid ID and AST assessments, respectively. To determine the potential impact of RP on antimicrobial therapy management, clinicians were interviewed on therapeutic decisions based on RP and SP results. RP accuracy, TAT and impact were evaluated in comparison to SP results.

Results. A total of 97 patients were enrolled. ID and AST concordance between RP and SP were 96.9 and 94.7 %, respectively. RP technical and real-life TAT were lower than SP (6.4 h vs. 18.4 h; 9.5 vs. 27.1 h). The agreement between RP- and SP-based therapeutic decisions was 90.7 (90 % CI 84.4–95.1). RP results could produce 24/97 correct antibiotic changes with 18/97 possible de-escalations and 25/97 prompt applications of infection control precautions.

Conclusion. With the application of RP in BSI management, about one-fourth of patients may safely benefit from early targeted antibiotic therapy and infection control policies with one working day in advance in comparison to conventional methods. This protocol is feasible for clinical use in microbiology laboratories and potentially helpful for Antimicrobial Stewardship.
Refined novel techniques for long term cryo-storage using vitrification and laser warming
Authors: Lin Chiahsin , Hsieh Wen-Chung , Loeslakwiboon Kanokpron , Huang Cheng-Liang , Chen Ting-Chun , Tsai Sujune
Published: January 2023

Vitrification and ultra-rapid laser warming technique is an important approach for cryopreservation of animal embryos and oocytes, as well as other cells with medicinal, genetic, and agricultural value. We believe that the long term cryo-storage after vitrification and for the following laser warming has only been achieved to date using our customized device which was first attempted to be developed in our study. In the present study, we focused on developing alignment and bonding techniques for special cryo-jig which were assembling jig tool and jig holder in one piece. This newly produced customized cryo-jig was demonstrated to have significantly high laser striking accuracy of 95% and a successful rewarming rate of 62%. This study was experimentally demonstrate an refined novel device for improvement of laser striking accuracy after long term cryo-storage using vitrification and laser warming technique. In addition, the customized device described herein was successfully applied to a biological sample with over a thousand coral larvae in long term cryo-storage (The first cryo-repository for coral larvae; the results related to coral cryobanking and repositry described in this preprint will be published separately in details). We anticipate that our core findings will provide further examples of cryobanking applications that use vitrification and nano-laser warming to help a wide range of cells and tissues from diverse species.
A Positive Response around 4.6 ms in Auditory Brainstem Response in Cochlear Nerve Deficiency Infants
Authors: Li Bei , Huang Meiping , Jiang Mengda , Shi Wentao , Wu Hao , Huang Zhiwu , Li Yun
Published: January 2023

Objectives

A positive response around 4.6 ms latency (IV’ wave) was observed at high intensity level in the ears which were always diagnosed with cochlear nerve deficiency (CND). This study is aimed to investigate the relationship between the IV’ wave and CND.

Study Design

Retrospective study.

Setting

Tertiary hospital

Methods

The raw Auditory Brainstem Response data and inner ear images of the infants were reviewed. Data were analyzed by ear and the CND ears were further divided into the IV’ wave present and IV’ wave absent group. The distortion product otoacoustic emissions (DPOAE) and auditory steady-state response (ASSR) results were compared between the two groups.

Results

In total, 570 ears were included. There were 129 ears diagnosed with CND and the IV’ wave was observed in 52 ears. The latency of the IV’ wave averaged 4.60 ms at 95 dB. The positive predictive value of the IV’ wave for CND was 98.1%. The incidence of the IV’ wave in the CND is highly unlikely to occur by chance. The differences of the DPOAE amplitude between the two groups were not significant. The ASSR results of the IV’ wave present group was significantly better.

Conclusions

Our study demonstrated a 4.6 ms positive response at high intensity level in the infants. The IV’ wave showed an excellent positive predictive value for CND. The extrapolated thresholds of the IV’ wave present group were better. The IV’ wave is expected to be a new indicator for the CND infants.
The Value of Admission Avoidance: Cost-Consequence Analysis of One-Year Activity in a Consolidated Service
Authors: Hernandez Carme , Herranz Carme , Baltaxe Erik , Seijas Nuria , González-Colom Rubèn , Asenjo Maria , Coloma Emmanuel , Fernandez Joaquim , Vela Emili , Carot-Sans Gerard , Cano Isaac , Roca Josep , Nicolas David
Published: January 2023

Background

Many advantages of hospital at home (HaH), as a modality of acute care, have been highlighted, but controversies exist regarding the cost-benefit trade-offs.

Objective

To assess health outcomes and analytical costs of hospital avoidance (HaH-HA) in a consolidated service with over ten years of delivery of HaH in Barcelona (Spain).

Methods

A retrospective cost-consequence analysis of all first episodes of HaH-HA, directly admitted from the emergency room (ER) in 2017–2018, was carried out. HaH-HA was compared with a propensity-score-matched group of contemporary patients admitted to conventional hospitalization (Controls). Mortality, re-admissions, ER visits, and direct healthcare costs were evaluated.

Registration

ClinicalTrials.gov(26/04/2017;NCT03130283).

Results

HaH-HA and Controls (n=441 each) were comparable in terms of age (73 [SD16]vs74 [16]), gender (male, 57%vs59%), multimorbidity, healthcare expenditure during the previous year, case mix index of the acute episode, and main diagnosis at discharge. HaH-HA presented lower mortality during the episode (0 vs. 19 (4.3%);p< 0.001). At 30 days post-discharge, HaH-HA and Controls showed similar re-admission rates; however, ER visits were lower in HaH-HA than in Controls (28 (6.3%) vs 34 (8.1%); p = 0.044). Average costs per patient during the episode were lower in the HaH-HA group (€ 1,078) than in Controls (€ 2,171). Likewise, healthcare costs within the 30 days post-discharge were also lower in HaH-Ha than in Controls (p< 0.001).

Conclusions

The study showed higher performance and cost reductions of HaH-HA in a real-world setting. The identification of sources of savings facilitates scaling of hospital avoidance.

Funding

This article was funded by JADECARE project- HP-JA-2019 - Grant Agreement nº951442 (2020-2023), a European Union’s Health Program 2014-2020.

KEY POINTS

Hospital at home, modality hospital avoidance, shows high potential for value generation in real-world settings by improving health outcomes and generating cost-savings.

Positive outcomes of hospital avoidance seem associated to adequate management change and digital support.
Counting Cells by Age Tells Us About How, and Why, and When, We Grow, and Become Old and Ill
Authors: Citi Luca , Su Jessica , Huang Luke , Michaelson James S
Published: January 2023

Growth and aging are fundamental features of animal life. The march from fertilization to oblivion comes in enormous variety: days and hundreds of cells for nematodes, decades and trillions of cells for humans.1-4Since Verhulst (18385) proposed the Logistic Equation - exponential growth with a countervailing linear decline in rate – biologists have searched for ever better density-dependent growth equations,6-12none of which accurately capture the relationship between size and time for real animals.13-15Furthermore, while growth and aging run in parallel, whether the relationship is causal has yet to be determined. Similarly unknown has been the reason behind the exponentialForce of Mortality, described by Gompertz in 1825 for all-cause mortality16and reported by Levin et al. in 2020 for COVID-19.17Here we report that examination in units of numbers of cells,N, Cellular Phylodynamic Analysis,6reveals that growth, lifespan, and mortality, are linked to the reduction in the fraction of cells dividing, occurring by a simple expression, theUniversal Mitotic Fraction Equation. Lifespan is correlated with an age when fewer than one-in-a-thousand cells are dividing, quantifying the long-appreciated mechanism of aging, the failure of cells to be rejuvenated by dilution with new materials made and DNA repaired at mitosis.29-31These observations provide practical mathematical tools for comprehending and managing the challenges of growth and aging, for such tasks as deciphering COVID-19 lethality and its amelioration by vaccination.
Heterogeneity of Glycan Biomarker Clusters as an Indicator of Recurrence in Pancreatic Cancer
Authors: Wisniewski Luke , Braak Samuel , Klamer Zachary , Gao ChongFeng , Shi Chanjuan , Allen Peter , Haab Brian B.
Published: January 2023

Outcomes following tumor resection vary dramatically among patients with pancreatic cancer. A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence. We probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block tumor sections. The tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells. Thus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome.
Changes in Plasma Fatty Acid Abundance Related to Chronic Pancreatitis: A Pilot Study
Authors: Gumpper-Fedus Kristyn , Crowe Olivia , Hart Phil A. , Pita-Grisanti Valentina , Velez-Bonet Ericka , Belury Martha A. , Ramsey Mitchell , Cole Rachel M , Badi Niharika , Culp Stacey , Hinton Alice , Lara Luis , Krishna Somashekar G. , Conwell Darwin L. , Cruz-Monserrate Zobeida
Published: January 2023

Objectives

Chronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance.

Methods

Blood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups.

Results

Decreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse.

Conclusions

Plasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.
Utilization and Factors Associated with Health Facility Delivery among Women of Reproductive Age in Rural Ethiopia: Mixed effect logistic regression analysis
Authors: Semagn Birhan Ewunu
Published: January 2023

Background

Worldwide over 800 women lose their life each day from complication in pregnancy and child birth. Inequity by urban–rural residence is one of the most pronounced challenges in maternal health service coverage with women living in rural areas at a greater disadvantage than other women. This study aims to assess the magnitude and factors affecting the utilization of health facility delivery for the most recent live birth among women of reproductive age in rural Ethiopia.

Methods

This is a cross-sectional study based on a data from Ethiopian Mini Demographic and Health Survey 2019 dataset with a total weighted sample of 2900 women of reproductive age group in rural Ethiopia. Data cleaning, coding and labeling were done using STATA version 14 software. Multilevel mixed effect logistic regression model was employed to identify associated factors.

Result

Only 44% of reproductive-age women in rural Ethiopia gave their most recent live birth in health institutions. In the multivariable multilevel binary logistic regression analysis educational status, wealth index, marital status, household family size, attending 4+ANC, had ANC in the first trimester of pregnancy and ANC by skilled provider were found to be statistically significant factors associated with health facility delivery.

Conclusion

In a rural part of Ethiopia, the prevalence of institutional delivery is low. Special emphasis should be given for mothers with no formal education, with poor household wealth index, married women, and mothers with more than five household family sizes. Furthermore implementing public health programs that target to enable women to have early first trimester Ante Natal Care, ANC by skilled provider and more frequent Ante Natal Care follow-up may increase the number of health facility deliveries.
Estimating clinical risk in gene regions from population sequencing cohort data
Authors: Fife James D. , Cassa Christopher A.
Published: January 2023

While pathogenic variants significantly increase disease risk in many genes, it is still challenging to estimate the clinical impact of rare missense variants more generally. Even in genes such asBRCA2orPALB2, large cohort studies find no significant association between breast cancer and rare germline missense variants collectively. Here we introduce REGatta, a method to improve the estimation of clinical risk in gene segments. We define gene regions using the density of pathogenic diagnostic reports, and then calculate the relative risk in each of these regions using 109,581 exome sequences from women in the UK Biobank. We apply this method in seven established breast cancer genes, and identify regions in each gene with statistically significant differences in breast cancer incidence for rare missense carriers. Even in genes with no significant difference at the gene level, this approach significantly separates rare missense variant carriers at higher or lower risk (BRCA2regional model OR=1.46 [1.12, 1.79], p=0.0036 vs.BRCA2gene model OR=0.96 [0.85,1.07] p=0.4171). We find high concordance between these regional risk estimates and high-throughput functional assays of variant impact. We compare with existing methods and the use of protein domains (Pfam) as regions, and find REGatta better identifies individuals at elevated or reduced risk. These regions provide useful priors which can potentially be used to improve risk assessment and clinical management.
DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts
Authors: Shumliakivska Mariana , Luxán Guillermo , Hemmerling Inga , Abplanalp Wesley Tyler , Li Xue , Scheller Marina , Müller-Tidow Carsten , Leuschner Florian , Schuhmacher Bianca , Debes Alisa , Glaser Simone-Franziska , Reinholz Marion Muhly , Kirschbaum Klara , Hoffmann Jedrzej , Nagel Eike , Puntmann Valentina O. , John David , Cremer Sebastian , Zeiher Andreas M. , Dimmeler Stefanie
Published: January 2023

Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A) drive clonal hematopoiesis of indeterminate potential (CHIP) and are associated with adverse prognosis in patients with heart failure (HF). The interactions between CHIP-mutated cells and other cardiac cell types remain unknown.

Here, we identify fibroblasts as potential interaction partners of CHIP-mutated monocytes using combined transcriptomic data from peripheral blood mononuclear cells of HF patients with and without CHIP and the cardiac tissue. We demonstrate that CHIP augments macrophage-to-cardiac fibroblasts interactions. Mechanistically, the secretome ofDNMT3A-silenced monocytes leads to myofibroblast activation, partially through epidermal growth factor (EGFR) signaling. Harboring DNMT3A CHIP-driver mutations is associated with increased cardiac interstitial fibrosis in mice and patients, and, thereby, may contribute to the poor outcome.

These findings not only identify a novel pathway of DNMT3A CHIP-driver mutation-induced instigation and progression of HF, but may also provide a rationale for the development of new anti-fibrotic strategies.

Graphical abstract
Break-induced replication is the primary recombination pathway in plant somatic hybrid mitochondria: a model for mt-HGT
Authors: Gandini Carolina L. , Garcia Laura E. , Abbona Cinthia C. , Ceriotti Luis F. , Kushnir Sergei , Geelen Danny , Sanchez-Puerta M. Virginia
Published: January 2023

Somatic hybrids between distant species offer a remarkable model to study genomic recombination events after mitochondrial fusion. Recently, our lab described highly chimeric mitogenomes in two somatic hybrids between the SolanaceaeNicotiana tabacumandHyoscyamus nigerresulting from interparental homologous recombination. To better examine the recombination map in somatic hybrid mitochondria, we developed a more sensitive bioinformatic strategy to detect recombination activity based on high-throughput sequencing without assembling the hybrid mitogenome. We generated a new intergeneric somatic hybrid and re-analyzed the two Solanaceae somatic hybrids. We inferred 213 homologous recombination events across repeats of 2.1 kb on average. Most of them (∼80%) were asymmetrical, consistent with the break-induced replication (BIR) pathway. Only rare (2.74%) non-homologous events were detected. Interestingly, independent events frequently occurred in the same regions within and across somatic hybrids, suggesting the existence of recombination hotspots in plant mitogenomes. BIR is the main pathway of interparental recombination in somatic hybrid mitochondria. Likewise, under the fusion compatibility model of mitochondrial horizontal transfer, foreign mitochondria fuse with those in the recipient cell and their genomes likely recombine via BIR, resulting in the integration and/or loss of mitochondrial DNA. Findings of this study are also relevant to mitogenome editing assays.

Highlight

We show that the chimeric mitochondrial genomes of somatic hybrids result from one of the three described homologous recombination pathways (BIR), mimicking the fusion compatibility model for plant HGT.
Fully automated detection of dendritic spines in 3D live cell imaging data using deep convolutional neural networks
Authors: Vogel Fabian W. , Alipek Sercan , Eppler Jens-Bastian , Triesch Jochen , Bissen Diane , Acker-Palmer Amparo , Rumpel Simon , Kaschube Matthias
Published: January 2023

Dendritic spines are considered a morphological proxy for excitatory synapses, rendering them a target of many different lines of research. Over recent years, it has become possible to image simultaneously large numbers of dendritic spines in 3D volumes of neural tissue. In contrast, currently no automated method for spine detection exists that comes close to the detection performance reached by human experts. However, exploiting such datasets requires new tools for the fully automated detection and analysis of large numbers of spines. Here, we developed an efficient analysis pipeline to detect large numbers of dendritic spines in volumetric fluorescence imaging data. The core of our pipeline is a deep convolutional neural network, which was pretrained on a general-purpose image library, and then optimized on the spine detection task. This transfer learning approach is data efficient while achieving a high detection precision. To train and validate the model we generated a labelled dataset using five human expert annotators to account for the variability in human spine detection. The pipeline enables fully automated dendritic spine detection and reaches a near human-level detection performance. Our method for spine detection is fast, accurate and robust, and thus well suited for large-scale datasets with thousands of spines. The code is easily applicable to new datasets, achieving high detection performance, even without any retraining or adjustment of model parameters.
VICTORY for Cryo-EM: Ultra-High Atomic Resolution Cryo-EM Structure of ß-Galactosidase at 1.1 Å
Authors: Chakraborty Arka
Published: January 2023

Withdrawal statement

This manuscript has been withdrawn owing to inclusion of false information, following a formal investigation by the Goethe University Frankfurt.
Moderating carbohydrate digestion rate promotes metabolic flexibility in mice
Authors: Hayes Anna M.R. , Swackhamer Clay , Quezada-Calvillo Roberto , Butte Nancy F. , Sterchi Erwin E. , Nichols Buford L. , Hamaker Bruce R.
Published: January 2023

Superior metabolic flexibility, or the ability to efficiently switch between oxidation of carbohydrate and fat, is inversely associated with obesity and type 2 diabetes. This study examined the impact of dietary carbohydrate digestion rate on metabolic substrate utilization and metabolic flexibility. We employed percent relative cumulative frequency (PRCF) analyses coupled with a new application of modeling using the Mixed Weibull Cumulative Distribution function to examine respiratory exchange ratio (RER) data from wild-type mice and mice lacking the mucosal maltase-glucoamylase enzyme (Mgam, null) under different dietary carbohydrate conditions. We further devised a Metabolic Flexibility Factor (MFF) to quantitate metabolic flexibility, with higher MFF indicating higher metabolic flexibility. The collective results indicated that a diet high in slowly digestible starch exhibited higher metabolic flexibility (MFF) than diets high in resistant starch, sucrose, or fat. These findings show a new-found benefit of consuming slowly digestible carbohydrates for improved metabolic health.
Comparative Transcriptome Profiling Provides Insights into the Growth Promotion Activity ofPseudomonas fluorescensstrain SLU99 in Tomato and Potato Plants
Authors: binti Hanifah Nurul Atilia Shafienaz , Ghadamgahi Farideh , Ghosh Samrat , Ortiz Rodomiro , Whisson Stephen C. , Vetukuri Ramesh R. , Kalyandurg Pruthvi B.
Published: January 2023

The use of biocontrol agents with plant growth-promoting activity has emerged as an approach to support sustainable agriculture. During our field evaluation of potato plants treated with biocontrol rhizobacteria, four bacteria were associated with increased plant height. Using two important solanaceous crop plants, tomato and potato, we carried out a comparative analysis of the growth-promoting activity of the four bacterial strains:Pseudomonas fluorescensSLU99,Serratia plymuthicaS412,S. rubidaeaAV10, andS. rubidaeaEV23. Greenhouse andin vitroexperiments showed thatP. fluorescensSLU99 promoted plant height, biomass accumulation, and yield of potato and tomato plants, while EV23 promoted growth in potato but not in tomato plants. SLU99 induced the expression of plant hormone-related genes in potato and tomato, especially those involved in maintaining homeostasis of auxin, cytokinin, gibberellic acid and ethylene. Our results reveal potential mechanisms underlying the growth promotion and biocontrol effects of these rhizobacteria and suggest which strains may be best deployed for sustainably improving crop yield.
Target complementarity in cnidarians supports a common origin for animal and plant microRNAs
Authors: Admoni Yael , Fridrich Arie , Razin Talya , Salinas-Saavedra Miguel , Rabani Michal , Frank Uri , Moran Yehu
Published: January 2023

microRNAs (miRNAs) are important post-transcriptional regulators that activate silencing mechanisms by annealing to mRNA transcripts. While plant miRNAs match their targets with nearly-full complementarity leading to mRNA cleavage, miRNAs in most animals require only a short sequence called ‘seed’ to inhibit target translation. Recent findings showed that miRNAs in cnidarians, early-branching metazoans, act similarly to plant miRNAs, by exhibiting full complementarity and target cleavage; however, it remained unknown if seed- based regulation was possible in cnidarians. Here, we investigate the miRNA-target complementarity requirements for miRNA activity in the cnidarianNematostella vectensis. We show that bilaterian-like complementarity of seed-only or seed and supplementary 3’ matches are insufficient for miRNA-mediated knockdown. Furthermore, miRNA-target mismatches in the cleavage site decrease knockdown efficiency. Finally, miRNA silencing of a target with three seed binding sites in the 3’ untranslated region that mimics typical miRNA targeting was repressed in zebrafish but not inNematostellaandHydractinia symbiolongicarpus. Altogether, these results unravel striking similarities between plant and cnidarian miRNAs consolidating the evidence for common evolutionary origin of miRNAs in plants and animals.