bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Expansion of the Healing Emotional Lives of Peers Program During COVID-19: A Second Victim Peer Support Program for Healthcare Professionals
Authors: Rivera-Chiauzzi Enid Y. , Huang Lily , Osborne Alayna K. , Musch Ashley A. , Berkland Bridget E. , Meyer Anne T. , Vitek Sairey M. , Wieneke Kaisa C. , Allyse Megan A. , Riggan Kirsten A. , Finney Robyn E.
Published: November 2023

Objectives

In 2018, the Healing Emotional Lives of Peers (HELP) Program was implemented at Mayo Clinic Rochester to guide healthcare professionals (HCPs) after a second victim experience, such as adverse patient events or medical errors. The HELP program was expanded to all HCPs in response to the anticipated stressors of the COVID-19 pandemic. This article aims to describe the rapid expansion of the peer support program and evaluate the effectiveness of peer support provided to affected colleagues (ACs).

Methods

Quantitative data collected from workshop evaluations, activations, and associated metrics (TPS Self-Assessment, Encounter Form, and AC Self-Assessment) were summarized through standard descriptive statistics using SAS version 9.4 software. Open-ended responses were qualitatively analyzed for iterative themes about the HELP program and associated workshops.

Results

Between April 2020 and December 2021, 22 virtual workshops to train peer supporters were conducted with 827 attendees. Of these, 464 employees completed the workshop evaluation. A total of 94.2% rated the workshop as excellent or very good. Participants perceived the workshop to be highly effective and felt more prepared to support ACs. Between May 2020 and December 2021, 247 activations were submitted through the HELP Program’s intranet Web site and peer support was requested for 649 employees. Of the 268 TPS Self-Assessments, 226 (84.3%) felt that they provided helpful support to an AC. One hundred ACs evaluated support received, with 93% being “extremely” or “very satisfied.” Affected colleagues appreciated having a TPS provide judgment-free support.

Conclusions

The HELP Program promotes a culture of safety by helping HCPs process traumatic events. To effectively meet the needs of patients, healthcare organizations need to prioritize the well-being of their employees through interpersonal support.
Initial antiretroviral therapy regimen and risk of heart failure
Authors: Silverberg Michael J. , Pimentel Noel , Leyden Wendy A. , Leong Thomas K. , Reynolds Kristi , Ambrosy Andrew P. , Towner William J. , Hechter Rulin C. , Horberg Michael , Vupputuri Suma , Harrison Teresa N. , Lea Alexandra N. , Sung Sue Hee , Go Alan S. , Neugebauer Romain
Published: November 2023

Objective(s):

Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk.

Design:

Cohort study.

Methods:

PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors.

Results:

Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5–4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2–1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1–0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5–5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P = 0.002).

Conclusion:

PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.
Effect of Laparoscopic and Open Pancreatoduodenectomy for Pancreatic or Periampullary Tumors
Authors: Qin Tingting , Zhang Hang , Pan Shutao , Liu Jun , Li Dewei , Chen Rufu , Huang Xiaobing , Liu Yahui , Liu Jianhua , Cheng Wei , Chen Xuemin , Zhao Wenxing , Li Jingdong , Tan Zhijian , Huang Heguang , Li Deyu , Zhu Feng , Yu Guangsheng , Zhou Baoyong , Zheng Shangyou , Tang Yichen , Ke Jianji , Liu Xueqing , Chen Botao , Chen Weibo , Ma Hongqin , Xu Jian , Liu Yifeng , Lin Ronggui , Dong Yadong , Yu Yahong , Wang Min , Qin Renyi ,   Minimally Invasive Treatment Group in the Pancreatic Disease Branch of China’s International Exchange and Promotion Association for Medicine and Healthcare (MITG-P-CPAM)
Published: November 2023

Objective:

This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors.

Summary Background Data:

LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD.

Methods:

This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year OS, quality of life, which was assessed using the 3-level version of the EQ-5D (EQ-5D-3L), depression, and other outcomes were evaluated.

Results:

Data from 656 patients (328 men [69.9%]; mean [SD] age: 56.2 [10.7] years) who underwent PD were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively (P=0.33, hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively (P=0.40, HR: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the two groups.

Conclusions:

In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD.
Influence of Preoperative Educational Intervention for Patients Undergoing Fecal Ostomy Surgery
Authors: García-Cabrera Ana María , de la Portilla de Juan Fernando , Navarro-Morales Laura , Ribera García Sebastián , Durán Ventura María del Carmen , Fernández Luque Inés , Padillo-Ruiz Francisco Javier
Published: November 2023

PURPOSE:

This aim of this study was to compare the impact on hospital stay and short-term overall complications prior to and following the introduction of an outpatient preoperative ostomy education program to an existing inpatient ostomy education program.

DESIGN:

A comparison cohort study.

SUBJECTS AND SETTING:

One hundred thirty-eight consecutive patients undergoing ostomy surgery were included. One group (n = 65, 47%) was given an experimental preoperative ostomy education intervention, along with standard care including a postoperative educational intervention during the initial hospital course. A second group (n = 73, 53%) received the same standardized education in the postoperative period. Data were collected from a single tertiary center located in Seville, Spain, during a 12-month period between July 2014 and June 2015.

METHODS:

Data were collected in 2 phases. Data from participants undergoing postoperative (standard) education were collected retrospectively. Data for the group receiving preoperative education were collective prospectively. Outcome variables were postoperative length of stay, surgical complications (severity was assessed by the Clavien-Dindo grading system), subsequent interventions, and readmission rates.

RESULTS:

Analysis indicated no differences between the average length of postoperative hospital stay (12.32 days in the preoperative education group vs 12.76 days in the postoperative education group, P = .401). In contrast, overall complications, mortality, and readmission rates were significantly higher in the preoperative education program group (P = .027, P = .047, and P = .046, respectively).

CONCLUSIONS:

Delivering a standardized educational intervention during the preoperative period versus postoperative education delivery during the ostomy surgery hospital course did not reduce length of stay. Analysis indicated that overall complications, mortality, and readmission rates were significantly higher in the preoperative education program group but we hypothesize that intervening factors may have influenced these outcomes.
Peristomal Moisture-Associated Skin Damage Treatment: Use of Cyanoacrylate Liquid Skin Protectant
Authors: Hill Rosemary H. , Smith Stephen L.
Published: November 2023

BACKGROUND:

Despite recent advances in ostomy care, the incidence of stoma and peristomal skin complications including peristomal moisture-associated skin damage (MASD) remains as high as 80% of patients living with ostomies. We evaluated a cyanoacrylate liquid skin protectant (CLSP) for the treatment and healing of peristomal MASD in patients with an ileostomy, ileal conduit, or colostomy.

CASES:

Five patients (24-85 years old) with peristomal MASD related to an ileostomy (n = 2), ileal conduit (n = 2), or colostomy (n = 1) were evaluated in this case study. All were treated with a CLSP in an attempt to reduce peristomal MASD caused by effluent leakage, which resulted in painful denudation of the peristomal skin. All patients received 1 to 2 applications of the CLSP prior to replacement of the pouching system. Prior to CLSP application, patients underwent assessment focusing on the causes of ostomy pouching system undermining and leakage. Interventions to prevent recurrent undermining and leakage, usually focused on modifications of the pouching system, were completed when indicated.

CONCLUSIONS:

For these 5 patients, complete resolution of peristomal MASD was observed at 2 to 8 days following CLSP treatment. More severe peristomal MASD cases required 7 to 8 days for complete resolution while less severe peristomal MASD resolved within 2 to 3 days. Patients showed less frequent pouching system changes, healing of peristomal skin, and reduced peristomal MASD associated with the CLSP treatment and addressing underlying etiology. On a pain scale of 0 to 10, patients reported less pain with an average of more than 7 out of 10 prior to the CLSP treatment and less than 4 out of 10 after treatment.
Antidepressants use in Italy: an ecological study of national and regional trends and associated factors
Authors: Amendola Simone , Hengartner Michael Pascal
Published: November 2023

The present study aimed to (1) provide an update on trends in AD consumption both at the national and regional unit of analysis for the period 2000–2020 in Italy and (2) analyze sociodemographic and healthcare system-related factors associated with AD prescribing at the regional-population level between 2000 and 2019. Data were extracted from reports of the Italian Medicines Agency and databases of the Italian National Institute of Statistics. Linear regression and mixed models were applied to analyze trends in AD use (DDD/1000/day) and ecological factors associated with AD prescribing. Between 2000 and 2010 AD prescription rates constantly increased. Thereafter they stabilized until 2017 when a positive trend began again. There was a positive ecological association between AD prescribing and rates of hospital discharge due to affective disorders, antibiotics prescribing, public non-drug healthcare spending per capita, and Northern regions compared to Southern regions. AD consumption increased massively during the 2000s, flattened during the 2010s but thereafter increased again until 2020. The ecological correlation between healthcare provision/spending and AD consumption suggests that health-economic factors may play an important role.
Microbiome and photoperiod interactively determine thermal sensitivity of polar and temperate diatoms
Authors: Giesler Jakob K. , Harder Tilmann , Wohlrab Sylke
Published: November 2023

The effect of temperature on ectothermic organisms in the context of climate change has long been considered in isolation (i.e. as a single driver). This is challenged by observations demonstrating that temperature-dependent growth is correlated to further factors. However, little is known how the chronobiological history of an organism reflected in its adaptation to re-occurring cyclic patterns in its environment (e.g. annual range of photoperiods in its habitat) and biotic interactions with its microbiome, contribute to shaping its realized niche. To address this, we conducted a full-factorial microcosm multi-stressor experiment with the marine diatoms
Thalassiosira gravida
(polar) and
Thalassiosira rotula
(temperate) across multiple levels of temperature (4°C; 9°C; 13.5°C) and photoperiod (4 h; 16 h; 24 h), both in the presence or absence of their microbiomes. While temperature-dependent growth of the temperate diatom was constrained by short and long photoperiods, the polar diatom coped with a 24 h photoperiod up to its thermal optimum (9°C). The algal microbiomes particularly supported host growth at the margins of their respective fundamental niches except for the combination of the warmest temperature tested at 24 h photoperiod. Overall, this study demonstrates that temperature tolerances may have evolved interactively and that the mutualistic effect of the microbiome can only be determined once the multifactorial abiotic niche is defined.
Symmetry in models of natural selection
Authors: Allen Benjamin
Published: November 2023

Symmetry arguments are frequently used—often implicitly—in mathematical modelling of natural selection. Symmetry simplifies the analysis of models and reduces the number of distinct population states to be considered. Here, I introduce a formal definition of symmetry in mathematical models of natural selection. This definition applies to a broad class of models that satisfy a minimal set of assumptions, using a framework developed in previous works. In this framework, population structure is represented by a set of sites at which alleles can live, and transitions occur via replacement of some alleles by copies of others. A symmetry is defined as a permutation of sites that preserves probabilities of replacement and mutation. The symmetries of a given selection process form a group, which acts on population states in a way that preserves the Markov chain representing selection. Applying classical results on group actions, I formally characterize the use of symmetry to reduce the states of this Markov chain, and obtain bounds on the number of states in the reduced chain.
An upright life, the postural stability of birds: a tensegrity system
Authors: Abourachid Anick , Chevallereau Christine , Pelletan Idriss , Wenger Philippe
Published: November 2023

Birds are so stable that they can rest and even sleep standing up. We propose that stable static balance is achieved by tensegrity. The rigid bones can be held together by tension in the tendons, allowing the system to stabilize under the action of gravity. We used the proportions of the bird's osteomuscular system to create a mathematical model. First, the extensor muscles and tendons of the leg are replaced by a single cable that follows the leg and is guided by joint pulleys. Analysis of the model shows that it can achieve balance. However, it does not match the biomechanical characteristics of the bird's body and is not stable. We then replaced the single cable with four cables, roughly corresponding to the extensor groups, and added a ligament loop at the knee. The model is then able to reach a stable equilibrium and the biomechanical characteristics are satisfied. Some of the anatomical features used in our model correspond to innovations unique to the avian lineage. We propose that tensegrity, which allows light and stable mechanical systems, is fundamental to the evolution of the avian body plan. It can also be used as an alternative model for bipedal robots.
Best of both worlds? Helpers in a cooperative fairy-wren assist most to breeding pairs that comprise a potential mate and a relative
Authors: Teunissen Niki , Fan Marie , Roast Michael J. , Hidalgo Aranzamendi Nataly , Kingma Sjouke A. , Peters Anne
Published: November 2023

In cooperative breeders, individuals forego independent reproduction and help others raise offspring. Helping is proposed to be driven by indirect benefits from raising relatives, and/or direct benefits from raising additional recruits or helping itself. We propose that consideration of social context is also important, in particular the characteristics of the breeding pair: helping may also serve to lighten the workload of—or maintain social bonds with—breeders (e.g. kin, potential mates) who in turn can offer benefits to helpers (e.g. prolonged nepotism, future mating, future production of relatives). Here, we test this hypothesis, while controlling for potential direct and indirect benefits from raising offspring, in purple-crowned fairy-wrens (
Malurus coronatus
) exhibiting variation in social group composition, and thus, breeder value. We show that helper provisioning rates to the nest were explained by characteristics of breeders that helpers assisted, rather than benefits from raising offspring. The presence of at least one related breeder was a prerequisite to help, but helpers provisioned most if assisting a relative
and
potential mate. Neglecting to take group composition into account would have led to misinterpretation of our results. A comprehensive understanding of the evolution of cooperative breeding hence requires nuanced consideration of social context.
Repeatability and heritability of inhibitory control performance in wild toutouwai (
Petroica longipes
)
Authors: McCallum Ella , Shaw Rachael C.
Published: November 2023

Despite increasing interest in the evolution of inhibitory control, few studies have examined the validity of widespread testing paradigms, the long-term repeatability and the heritability of this cognitive ability in the wild. We investigated these aspects in the inhibitory control performance of wild toutouwai (North Island robin;
Petroica longipes
), using detour and reversal learning tasks. We assessed convergent validity by testing whether individual performance correlated across detour and reversal learning tasks. We then further evaluated task validity by examining whether individual performance was confounded by non-cognitive factors. We tested a subset of subjects twice in each task to estimate the repeatability of performance across a 1-year period. Finally, we used a population pedigree to estimate the heritability of task performance. Individual performance was unrelated across detour and reversal learning tasks, indicating that these measured different cognitive abilities. Task performance was not influenced by body condition, boldness or prior experience, and showed moderate between-year repeatability. Yet despite this individual consistency, we found no evidence that task performance was heritable. Our findings suggest that detour and reversal learning tasks measure consistent individual differences in distinct forms of inhibitory control in toutouwai, but this variation may be environmentally determined rather than genetic.
Plane and axisymmetric problems of an interfacial crack in a power-law graded material
Authors: Antipov Y. A.
Published: November 2023

Plane and axisymmetric problems of interfacial cracks in a power-law graded infinite medium are examined. It is shown that the models are governed by integral equations of Mellin’s convolution type whose kernels are expressed through the hypergeometric function. Exact solutions are derived by the method of orthogonal Jacobi polynomials in a series form and by the Wiener–Hopf method by quadratures. Mode-I stress intensity factors and the associated weight functions for power-law graded materials in the plane and axisymmetric cases are introduced and evaluated. It is shown that, although the displacement jump and the normal traction component have power singularities at the crack tip different from 1/2, the strain energy variation is proportional to the crack length change as in the case of homogeneous materials. A Griffith-type criterion of crack propagation in power-law graded materials is proposed and results of numerical tests are reported.
The macroevolutionary dynamics of mammalian sexual size dimorphism
Authors: Jones Megan E. , Sheard Catherine
Published: November 2023

Sexual size dimorphism (SSD) is a common phenomenon across the animal kingdom. Mammals are unusual in primarily displaying male-biased SSD, where males of a species are typically larger than females. The driving factors behind the evolution of this SSD have been much debated, with popular hypotheses invoking the influence of mating system and social organization via sexual selection, dietary niche divergence and broad-scale correlations with body size (Rensch's rule). Here, we investigate the macroevolutionary origins and maintenance of SSD among mammals, using phylogenetic general mixed linear models and a comprehensive global dataset to evaluate correlations of diet, body mass, seasonality, social organization and mating system with SSD type. We find that SSD as a whole is lost at a greater rate than it is gained, with female-biased SSD being particularly unstable. Non-monogamous mating systems, vertebrate prey consumption and temperature seasonality correlate with male-biased SSD, while polyandry correlates with female-biased SSD, and both types of SSD are positively correlated with body mass. This is in partial contrast to the predictions of Rensch's rule, which predicts that female-biased SSD would correlate negatively with body size. Taken together, our results highlight the importance of considering multiple ecological and social drivers when evaluating the macroevolutionary trajectory of sex differences in body size.
Environmental, sex-specific and genetic determinants of infant social behaviour in a wild primate
Authors: Lange Elizabeth C. , Griffin Madison , Fogel Arielle S. , Archie Elizabeth A. , Tung Jenny , Alberts Susan C.
Published: November 2023

Affiliative social bonds are linked to fitness components in many social mammals. However, despite their importance, little is known about how the tendency to form social bonds develops in young animals, or if the timing of development is heritable and thus can evolve. Using four decades of longitudinal observational data from a wild baboon population, we assessed the environmental determinants of an important social developmental milestone in baboons—the age at which a young animal first grooms a conspecific—and we assessed how the rates at which offspring groom their mothers develops during the juvenile period. We found that grooming development differs between the sexes: female infants groom at an earlier age and reach equal rates of grooming with their mother earlier than males. We also found that age at first grooming for both sexes is weakly heritable (
h
2
= 0.043, 95% CI: 0.002–0.110). These results show that sex differences in grooming emerge at a young age; that strong, equitable social relationships between mothers and daughters begin very early in life; and that age at first grooming is heritable and therefore can be shaped by natural selection.
Thermobacterium salinum gen. nov., sp. nov., a novel member of the family Flavobacteriaceae isolated from a hydrothermal zone
Authors: Chen Beihan , Zhang Haichen , Lin Dan , Ye Jianing , Tang Kai
Published: November 2023

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain, designated as strain TK19130T, was isolated from the Lonqi hydrothermal zone in the Southwest Indian Ridge. Growth occurred with 1–12 % (w/v) NaCl (optimum, 2–4 %), at 10–40 °C (optimum, 30–35 °C) and at pH 6.0–9.0 (optimum, pH 7.0–8.0). The genome of strain TK19130T was 3.15 Mb, with a DNA G+C content of 41.35 %. Based on the results of 16S rRNA gene sequence analysis, strain TK19130T was affiliated with the family

Flavobacteriaceae

, in which the highest similarity was 90.54 % to

Aureisphaera salina

A6D-50T, under the genus demarcation boundary (94.50 %). Average nucleotide identity values between strain TK19130T and adjacent strains were 67.17–72.00 %, lower than the recommended threshold of 73.98 % for genus delineation. The predominant respiratory quinone of strain TK19130T was menaquinone 6. Major polar lipids were phosphatidylethanolamine, three aminolipids and one unidentified polar lipid. Major fatty acids were detected as iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. Based on the polyphasic taxonomic evidence presented above, strain TK19130T formed an independent branch representing a new species of a novel genus within the family

Flavobacteriaceae

, for which the name Thermobacterium salinum gen. nov., sp. nov. is proposed. The type strain is TK19130T (=CGMCC 1.18993T=JCM 35842T=MCCC M28200T).
Local field potential sharp waves with diversified impact on cortical neuronal encoding of haptic input
Authors: Kristensen Sofie S. , Jörntell Henrik
Published: November 2023

Cortical sensory processing is greatly impacted by internally generated activity. But controlling for that activity is difficult since the thalamocortical network is a high-dimensional system with rapid state changes. Therefore, to unwind the cortical computational architecture there is a need for physiological ‘landmarks’ that can be used as frames of reference for computational state. Here we use a waveshape transform method to identify conspicuous local field potential sharp waves (LFP-SPWs) in the somatosensory cortex (S1). LFP-SPW events triggered short-lasting but massive neuronal activation in all recorded neurons with a subset of neurons initiating their activation up to 20 ms before the LFP-SPW onset. In contrast, LFP-SPWs differentially impacted the neuronal spike responses to ensuing tactile inputs, depressing the tactile responses in some neurons and enhancing them in others. When LFP-SPWs coactivated with more distant ECoG-SPWs, suggesting an involvement of these SPWs in global cortical signaling, the impact of the LFP-SPW on the neuronal tactile response could change substantially, including inverting its impact to the opposite. These cortical SPWs had similar overall activity patterns as reported for hippocampal SPWs and may be a biomarker for a particular type of state change that possibly involves both hippocampus and neocortex.
Proteome-wide base editor screens to assess phosphorylation site functionality in high-throughput
Authors: Kennedy Patrick H , Deh Sheikh Amin Alborzian , Balakar Matthew , Jones Alexander C , Olive Meagan E , Hegde Mudra , Matias Maria I , Pirete Natan , Burt Rajan , Levy Jonathan , Little Tamia , Hogan Patrick G , Liu David R , Doench John G , Newton Alexandra C , Gottschalk Rachel A. , de Boer Carl , Alarcón Suzie , Newby Gregory , Myers Samuel A.
Published: November 2023

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here, we describe “signaling-to-transcription network” mapping through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally-resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of the phosphatase PHLPP1 which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.
Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart
Authors: Stüdemann Tim , Schwarzova Barbora , Schneidewind Till , Geertz Birgit , von Bibra Constantin , Nehring Marie , Rössinger Judith , Wiegert J. Simon , Eschenhagen Thomas , Weinberger Florian
Published: November 2023

Transplantation of pluripotent stem cell-derived cardiomyocytes is a novel promising cell-based therapeutic approach for patients with heart failure. However, engraftment arrhythmias are a predictable life-threatening complication and represent a major hurdle for clinical translation. Catheter-based electrophysiological analysis suggested that the ventricular arrhythmias were caused by an automaticity of the transplanted cells, but whether impulse generation by transplanted cardiomyocytes can propagate to the host myocardium and override the recipient rhythm has not been directly assessed experimentally. We used optogenetics to specifically activate engrafted cardiomyocytes, which resulted in impulse generation in the engrafted cardiomyocytes and stimulated the recipient heart (4/9 hearts). Thus, our study shows that transplanted cardiomyocytes can electrically couple to the host myocardium and stimulate the recipient heart, providing experimental evidence that cardiomyocyte automaticity can serve as a trigger for ventricular arrhythmias.
From Data to Insights: Machine Learning Empowers Prognostic Biomarker Prediction in Autism
Authors: Mehmetbeyoglu Ecmel , Duman Abdulkerim , Taheri Serpil , Ozkul Yusuf , Rassaulzadegan Minoo
Published: November 2023

Autism Spectrum Disorder (ASD) poses significant challenges to society and science due to its impact on communication, social interaction, and repetitive behaviour patterns in affected children. The Autism and Developmental Disabilities Monitoring (ADDM) Network continuously monitors ASD prevalence and characteristics. In 2020, ASD prevalence was estimated at one in 36 children, with higher rates than previous estimates. This study focuses on ongoing ASD research conducted by Erciyes University. Serum samples from 45 ASD patients and 21 unrelated control participants were analysed to assess the expression of 372 microRNAs (miRNAs). Six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) exhibited significant downregulation in all ASD patients compared to healthy controls. The current study endeavours to identify dependable diagnostic biomarkers for ASD, addressing the pressing need for non-invasive, accurate, and cost-effective diagnostic tools, as current methods are subjective and time intensive. A pivotal discovery in this study is the potential diagnostic value of miR-126-3p, offering the promise of earlier and more accurate ASD diagnoses, potentially leading to improved intervention outcomes. Leveraging machine learning, such as the K-nearest neighbours (KNN) model, presents a promising avenue for precise ASD diagnosis using miRNA biomarkers.
Rapid meiotic prophase chromosome movements inArabidopsis thalianaare linked to essential reorganization at the nuclear envelope
Authors: Cromer Laurence , Tiscareno-Andrade Mariana , Lefranc Sandrine , Chambon Aurélie , Hurel Aurélie , Brogniez Manon , Guérin Julie , Masson Ivan Le , Adam Gabrielle , Charif Delphine , Andrey Philippe , Grelon Mathilde
Published: November 2023

Meiotic rapid prophase chromosome movements (RPMs) require connections between the chromosomes and the cytoskeleton, involving SUN (Sad1/UNC-84)-domain-containing proteins at the inner nuclear envelope (NE). RPMs remain significantly understudied in plants, notably with respect to their importance in the regulation of meiosis. Here, we demonstrate thatArabidopsis thalianameiotic centromeres undergo rapid (up to 500 nm/s) and uncoordinated movements during the zygotene and pachytene stages. RPMs are not affected by altered chromosome organization and recombination but are abolished in the double mutantsun1 sun2. We also document the changes in chromosome dynamics and nucleus organization during the transition from leptotene to zygotene, including telomere attachment to SUN-enriched NE domains, bouquet formation, and nucleolus displacement, all of which were defective insun1 sun2. These results establishA. thalianaas a new model species for studying the functional implications of meiotic RPMs and demonstrate the mechanistic conservation of telomere-led RPMs in plants.
Non-synaptic plasticity enables memory-dependent local learning
Authors: Romain Ferrand , Maximilian Baronig , Florian Unger , Robert Legenstein
Published: November 2023

Synaptic plasticity is essential for memory formation and learning in the brain. In addition, recent results indicate that non-synaptic plasticity processes such as the regulation of neural membrane properties contribute to memory formation, its functional role in memory and learning has however remained elusive. Here, we propose that non-synaptic and synaptic plasticity are both essential components to enable memory-dependent processing in neuronal networks. While the former acts on a fast time scale for rapid information storage, the latter shapes network processing on a slower time scale to harness this memory as a functional component. We analyse this concept in a network model where pyramidal neurons regulate their apical trunk excitability in a Hebbian manner. We find that local synaptic plasticity rules can be derived for this model and show that the interplay between this synaptic plasticity and the non-synaptic trunk plasticity enables the model to successfully accommodate memory-dependent processing capabilities in a number of tasks, ranging from simple memory tests to question answering. The model can also explain contextual fear conditioning experiments, where freezing responses could be recovered by optogenetic reactivation of memory engrams under amnesia.

Author summary

How memory is organized in the brain in order to enable cognitive processing is a central open question in systems neuroscience. Traditionally, synaptic plasticity is considered the key mechanism for the establishment of memory in the brain. Recently however, this view has been questioned, and it was proposed that non-synaptic plasticity mechanisms play a more prominent role as previously considered. In this article, we propose that both, synaptic and non-synaptic plasticity are central components for the formation and utilization of memory in biological neuronal networks. Our results show that non-synaptic plasticity can act on a fast time-scale to store important information, while synaptic plasticity can adapt network function on a slow time scale in order to facilitate memory-dependent cognitive processing.
The development of the adult nervous system in the annelidOwenia fusiformis
Authors: Carrillo-Baltodano Allan M. , Donnellan Rory , Williams Elizabeth A. , Jékely Gáspar , Martín-Durán José M.
Published: November 2023

Background

The evolutionary origins of animal nervous systems remain contentious because we still have a limited understanding of neural development in most major animal clades. Annelids — a species-rich group with centralised nervous systems — have played central roles in hypotheses about the origins of animal nervous systems. However, most studies have focused on adults of deeply nested species in the annelid tree. Recently,Owenia fusiformishas emerged as an informative species to reconstruct ancestral traits in Annelida, given its phylogenetic position within the sister clade to all remaining annelids.

Methods

Combining immunohistochemistry of the conserved neuropeptides FVamide-lir, RYamide-lir, RGWamide-lir and MIP-lir with gene expression, we comprehensively characterise neural development from larva to adulthood inOwenia fusiformis.

Results

The early larval nervous system comprises a neuropeptide-rich apical organ connected through peripheral nerves to a prototroch ring and the chaetal sac. There are seven sensory neurons in the prototroch. A bilobed brain forms below the apical organ and connects to the ventral nerve cord of the developing juvenile. During metamorphosis, the brain compresses, becoming ring-shaped, and the trunk nervous system develops several longitudinal cords and segmented lateral nerves.

Conclusions

Our findings reveal the formation and reorganisation of the nervous system during the life cycle ofO. fusiformis, an early-branching annelid. Despite its apparent neuroanatomical simplicity, this species has a diverse peptidergic nervous system, exhibiting morphological similarities with other annelids, particularly at the larval stages. Our work supports the importance of neuropeptides in animal nervous systems and the evolution of biphasic life cycles.
Acentric chromosome congression and alignment on the metaphase plate via kinetochore-independent forces inDrosophila
Authors: Vicars Hannah , Karg Travis , Mills Alison , Sullivan William
Published: November 2023

Chromosome congression and alignment on the metaphase plate involves lateral and microtubule plus-end interactions with the kinetochore. Here we take advantage of our ability to efficiently generate a GFP-marked acentric X chromosome fragment inDrosophilaneuroblasts to identify forces acting on chromosome arms that drive congression and alignment. We find acentrics efficiently align on the metaphase plate, often more rapidly than kinetochore-bearing chromosomes. Unlike intact chromosomes, the paired sister acentrics oscillate as they move to and reside on the metaphase plate in a plane distinct and significantly further from the main mass of intact chromosomes. Consequently, at anaphase onset acentrics are oriented either parallel or perpendicular to the spindle. Parallel-oriented sisters separate by sliding while those oriented perpendicularly separate via unzipping. This oscillation, together with the fact that in monopolar spindles acentrics are rapidly shunted away from the poles, indicates that distributed plus-end directed forces are primarily responsible for acentric migration. This conclusion is supported by the observation that reduction of EB1 preferentially disrupts acentric alignment. In addition, reduction of Klp3a activity, a gene required for the establishment of pole-to-pole microtubules, preferentially disrupts acentric alignment. Taken together these studies suggest that plus-end forces mediated by the outer pole-to-pole microtubules are primarily responsible for acentric metaphase alignment. Surprisingly, we find that a small fraction of sister acentrics are anti-parallel aligned indicating that the kinetochore is required to ensure parallel alignment of sister chromatids. Finally, we find induction of acentric chromosome fragments results in a global reorganization of the congressed chromosomes into a torus configuration.

Article Summary

The kinetochore serves as a site for attaching microtubules and allows for successful alignment, separation, and segregation of replicated sister chromosomes during cell division. However, previous studies have revealed that sister chromosomes without kinetochores (acentrics) often align to the metaphase plate, undergo separation and segregation, and are properly transmitted to daughter cells. In this study, we discuss the forces acting on chromosomes, independent of the kinetochore, underlying their successful alignment in early mitosis.
Targeted Metagenomic Databases Provide Improved Analysis of Microbiota Samples
Authors: Baud Agnes , Kennedy Sean P
Published: November 2023

We introduceMoonbase, a flexible pipeline that can be used to build targeted, project-specific, databases in order to improve the accuracy of taxonomic detection and quantification in complex microbial communities.Moonbasewas evaluated using synthetic metagenomic samples and compared against existing methods including MetaPhlAn3 and generalized Kraken2 databases. Our results indicate thatMoonbasesignificantly improves species precision and quantification, outperforming marker genes and generalized databases. Construction of a phylogenetic tree from 16S data of genomes inMoonbaseallows for the incorporation of UniFrac-type phylogenetic information into diversity calculations of samples. We demonstrate the resulting analysis has increased statistical power in distinguishing microbial communities. This study highlights the continual evolution of metagenomic tools with the goal of improving metagenomic analysis and highlights the potential of theMoonbasepipeline.
RFX6haploinsufficiency predisposes to diabetes through impaired beta cell functionality
Authors: Ibrahim Hazem , Balboa Diego , Saarimäki-Vire Jonna , Montaser Hossam , Dyachok Oleg , Lund Per-Eric , Omar-Hmeadi Muhmmad , Kvist Jouni , Dwivedi Om Prakash , Lithovius Väinö , Barsby Tom , Chandra Vikash , Eurola Solja , Ustinov Jarkko , Tuomi Tiinamaija , Miettinen Päivi J. , Barg Sebastian , Tengholm Anders , Otonkoski Timo
Published: November 2023

Regulatory factor X 6 (RFX6) is indispensable for pancreatic endocrine development and differentiation. The RFX6 protein-truncating variant p.His293LeufsTer7 is significantly enriched in the Finnish population with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 diabetes (T2D) and gestational diabetes. To understand the role of this variant in β-cell development and function, we generated allelic series of isogenic pluripotent stem cell models and directed them into pancreatic islet lineages (SC-islets). Expectedly,in-vitromodels of the homozygousRFX6−/−variant failed to generate pancreatic endocrine cells, recapitulating the phenotype in Mitchell-Riley syndrome. Notably, heterozygousRFX6+/−derived SC-islets showed reduced β-cell maturation markers and calcium oscillations, resulting in defective insulin secretion, without affecting β-cell number or insulin content. The reduced insulin secretion is sustained duringin-vivoimplantation studies, consistent with the susceptibility of the carriers to develop diabetes.

Teaser

ModelingRFX6-assocciated neonatal and type-2 diabetes using allelic series stem cell-derived isletsin-vitroandin-vivo.
Comeback or evolution? Examining organizational resilience literature in pre and during COVID-19
Authors: Paeffgen Thea , Lehmann Tine , Feseker Mareike
Published: November 2023

Purpose

The ability of companies to develop organizational resilience before, during and after crises is crucial for their development and growth. The future forecasts increasingly more crises, thus this paper aims at identifying key topics around organizational resilience in COVID-19 times, differentiating them of pre-crisis literature and synthesizing them into a research framework.

Design/methodology/approach

Based on Web of Science and Scopus, the authors analysed the content of the only twenty-seven VHB-ranked primary studies discussing organizational resilience during COVID-19, providing a complete survey of this research area.

Findings

Following a content analysis, the authors identified main topics of interest for researchers at the moment of COVID-19, how it differed from before this adversity and provide an outlook on future research. The results presented include in the COVID-19 context: an adapted definition of organizational resilience, key theoretical framework, insights for future research. Some topics have been found to be increasingly more important during COVID-19 (i.e. digitalization, partnerships and learning) while others have been less explored although present in pre-COVID-19 research on organizational resilience (i.e. dynamic capabilities, anticipation and preparedness).

Originality/value

Understanding key issues in global disruptions could help practitioners in fostering resilience as much as researchers in identifying new ways to advance and maintain resilience. This paper differs from other reviews by providing a full text analysis, based on qualitative content analysis, of all ranked published papers in the considered period.
Voronoi discretization to improve the meshless local Petrov–Galerkin method in 3D-computational fracture mechanics
Authors: Ariannezhad Behrooz , Shahrooi Shahram , Shishesaz Mohammad
Published: November 2023

Purpose

1) The OE-MLPG penalty meshfree method is developed to solve cracked structure.(2) Smartening the numerical meshfree method by combining the particle swarm optimization (PSO) optimization algorithms and Voronoi computational geometric algorithm. (3). Selection of base functions, finding optimal penalty factor and distribution of appropriate nodal points to the accuracy of calculation in the meshless local Petrov–Galekrin (MLPG) meshless method.

Design/methodology/approach

Using appropriate shape functions and distribution of nodal points in local domains and sub-domains and choosing an approximation or interpolation method has an effective role in the application of meshless methods for the analysis of computational fracture mechanics problems, especially problems with geometric discontinuity and cracks. In this research, computational geometry technique, based on the Voronoi diagram (VD) and Delaunay triangulation and PSO algorithm, are used to distribute nodal points in the sub-domain of analysis (crack line and around it on the crack plane).

Findings

By doing this process, the problems caused by too closeness of nodal points in computationally sensitive areas that exist in general methods of nodal point distribution are also solved. Comparing the effect of the number of sentences of basic functions and their order in the definition of shape functions, performing the mono-objective PSO algorithm to find the penalty factor, the coefficient, convergence, arrangement of nodal points during the three stages of VD implementation and the accuracy of the answers found indicates, the efficiency of V-E-MLPG method with Ns = 7 and ß = 0.0037–0.0075 to estimation of 3D-stress intensity factors (3D-SIFs) in computational fracture mechanics.

Originality/value

The present manuscript is a continuation of the studies (Ref. [33]) carried out by the authors, about; feasibility assessment, improvement and solution of challenges, introduction of more capacities and capabilities of the numerical MLPG method have been used. In order to validate the modeling and accuracy of calculations, the results have been compared with the findings of reference article [34] and [35].