bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic anatomical segmentectomy: A paradigm shift towards minimally invasive liver surgery in Nepal: A cohort study
Authors: Ghimire Roshan , Mishra Aakash , Limbu Yugal , Regmee Sujan , Maharjan Dhiresh Kumar , Thapa Prabin Bikram
Published: April 2023

Introduction:

Laparoscopic liver resection is taking stride in slowly replacing open surgeries for various hepatic pathologies in many developed countries. However, due to high cost and lack of expertise, there are only a handful of centres in the low-medium income countries who perform advanced laparoscopic liver resections regularly. In this study, a prospective analysis was carried out to assess and report the outcomes of laparoscopic anatomical segmentectomy (LAS) from a single centre in Nepal.

Methods:

The clinical data of all patients who underwent LAS between 1 October 2021 to 30 September 2022 were prospectively recorded. Demographics, pathological diagnoses, types of resections performed, perioperative parameters, postoperative length of stay, postoperative complications data and IWATE score were collected and analyzed. All operations were performed using the extrahepatic Glissonean technique with the use of indocyanine green dye as an adjunct during the intraoperative period.

Results:

In the study period, a total of 16 LAS were performed in our centre for various indications. The mean age of the patients in the series was 41.6 years, and seven of 16 patients were male. The majority of the cases were segment 2/3 resection indicated for various pathologies and segment 4b/5 indicated for carcinoma gallbladder. The median hospital stay was 6 days and only two cases developed major complication. There were no mortalities in our series.

Conclusions:

Taking into account the results produced from a single centre in a low-medium income country, laparoscopic anatomical segmentectomy is technically feasible with an acceptable safety profile.
Sense of Coherence at End of Life in Older People
Authors: Gagne-Henderson Rebecca , Holland Carol , Walshe Catherine
Published: April 2023

As people age, losses accumulate (ie, the death of family and friends, the loss of agility, and the loss of independence). Such losses have an impact on one's Sense of Coherence, that is, one's ability to see the world as comprehensible, manageable, and meaningful. Antonovsky deemed Sense of Coherence as a mostly stable state by the age of 30 years. Until now, there has not been an investigation into how serial loss of resources affects older people as they near the end of life. Sense of Coherence was used as the theoretical framework for this study to answer the question of how older people maintain or regain a Sense of Coherence in the presence of serious illness as they near death. Data were gathered using semistructured interviews and guided by interpretive description. This investigation found new concepts that contribute to Antonovsky's midlevel theory of salutogenesis and the construct of Sense of Coherence. Those are Incomprehensibility and Serial Loss of General Resistance Resources. The results indicate that the crux of a strong Sense of Coherence for this population is excellent communication and a coherent “big-picture” conversation.
Time, Technology, Social Support, and Cardiovascular Health of Emerging Adults With Type 1 Diabetes
Authors: McCarthy Margaret M. , Yan Joeyee , Jared Mary Christine , Ilkowitz Jeniece , Gallagher Mary Pat , Dickson Victoria Vaughan
Published: April 2023

Background

Emerging adults with Type 1 diabetes (T1DM) face an increased risk of cardiovascular disease; however, there are both barriers and facilitators to achieving ideal cardiovascular health in this stage of their lives.

Objectives

The aim of this study was to qualitatively explore the barriers and facilitators of achieving ideal levels of cardiovascular health in a sample of emerging adults with T1DM ages 18–26 years.

Methods

A sequential mixed-methods design was used to explore achievement of ideal cardiovascular health using the seven factors defined by the American Heart Association (smoking status, body mass index, physical activity, healthy diet, total cholesterol, blood pressure, and hemoglobin A1C [substituted for fasting blood glucose]). We assessed the frequency of achieving ideal levels of each cardiovascular health factor. Using Pender’s health promotion model as a framework, qualitative interviews explored the barriers and facilitators of achieving ideal levels of each factor of cardiovascular health.

Results

The sample was mostly female. Their age range was 18–26 years, with a diabetes duration between 1 and 20 years. The three factors that had the lowest achievement were a healthy diet, physical activity at recommended levels, and hemoglobin A1C of <7%. Participants described lack of time as a barrier to eating healthy, being physically active, and maintaining in-range blood glucose levels. Facilitators included the use of technology in helping to achieve in-range blood glucose and social support from family, friends, and healthcare providers in maintaining several healthy habits.

Discussion

These qualitative data provide insight into how emerging adults attempt to manage their T1DM and cardiovascular health. Healthcare providers have an important role in supporting these patients in establishing ideal cardiovascular health at an early age.
Scoping Review of Early Toxic Stress and Epigenetic Alterations in the Neonatal Intensive Care Unit
Authors: Malin Kathryn J. , Gondwe Kaboni W. , Fial Alissa V. , Moore Rachel , Conley Yvette , White-Traut Rosemary , Griffith Thao
Published: April 2023

Background

Preterm infants are uniquely vulnerable to early toxic stress exposure while in the neonatal intensive care unit (NICU) and also being at risk for suboptimal neurodevelopmental outcomes. However, the complex biological mechanisms responsible for variations in preterm infants’ neurodevelopmental outcomes because of early toxic stress exposure in the NICU remain unknown. Innovative preterm behavioral epigenetics research offers a possible mechanism and describes how early toxic stress exposure may lead to epigenetic alterations, potentially affecting short- and long-term outcomes.

Objective

The aim of this study was to review the relationships between early toxic stress exposures in the NICU and epigenetic alterations in preterm infants. The measurement of early toxic stress exposure in the NICU and effect of epigenetic alterations on neurodevelopmental outcomes in preterm infants were also examined.

Methods

We conducted a scoping review of the literature published between January 2011 and December 2021 using databases PubMed, CINAHL, Cochrance Library, PsycINFO, and Web of Science. Primary data-based research that examined epigenetics, stress, and preterm infants or NICU were included.

Results

A total of 13 articles from nine studies were included. DNA methylations of six specific genes were studied in relation to early toxic stress exposure in the NICU: SLC6A4, SLC6A3, OPRMI, NR3C1, HSD11B2, and PLAGL1. These genes are responsible for regulating serotonin, dopamine, and cortisol. Poorer neurodevelopmental outcomes were associated with alterations in DNA methylation of SLC6A4, NR3C1, and HSD11B2. Measurements of early toxic stress exposure in the NICU were inconsistent among the studies.

Discussion

Epigenetic alterations secondary to early toxic stress exposures in the NICU may be associated with future neurodevelopmental outcomes in preterm infants. Common data elements of toxic stress exposure in preterm infants are needed. Identification of the epigenome and mechanisms by which early toxic stress exposure leads to epigenetic alterations in this vulnerable population will provide evidence to design and test individualized intervention.
Distinct Profiles of Morning and Evening Fatigue Co-Occurrence in Patients During Chemotherapy
Authors: Wright Fay , Cooper Bruce A. , Paul Steven M. , Hammer Marilyn J. , Conley Yvette P. , Levine Jon D. , Miaskowski Christine , Kober Kord M.
Published: April 2023

Background

Morning and evening fatigue are distinct and distressing symptoms experienced during chemotherapy that demonstrate a large amount of interindividual variability.

Objectives

The objectives of this study were to identify subgroups of patients with distinct morning and evening fatigue co-occurrence profiles and evaluate for differences among these subgroups in demographic, clinical, and symptom characteristics and quality of life.

Methods

Oncology patients (n = 1,334) completed the Lee Fatigue Scale to self-report morning and evening fatigue, six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct morning and evening physical fatigue profiles.

Results

Four distinct morning and evening fatigue profiles were identified (i.e., Both Low, Low Morning + Moderate Evening, Both Moderate, and Both High). Compared to the Both Low profile, the Both High profile was significantly younger, less likely to be married or partnered, more likely to live alone, had a higher comorbidity burden, and lower functional status. The Both High profile had higher levels of anxiety, depressive symptoms, sleep disturbance, and pain and lower levels of quality of life.

Discussion

The variability in the morning and evening severity scores among the four profiles supports the hypothesis that morning and evening fatigue are distinct but related symptoms. Clinically meaningful levels of both morning and evening fatigue were reported by 50.4% of our sample, which suggests that the co-occurrence of these two symptoms is relatively common. Patients in Both Moderate and Both High profiles experienced an extremely high symptom burden that warrants ongoing assessments and aggressive symptom management interventions.
Hair Collection for Cortisol Among Youth Experiencing Homelessness
Authors: Ford Jodi L. , Slesnick Natasha , Kelleher Kelly , Brakenhoff Brittany , Chavez Laura , Feng Xin , Mallory Allen , Moore Laura , O’Connor Rachel , Pinkus Lia , Sullenbarger Brent , Yilmazer Tansel , Zavarella Haylie
Published: April 2023

Background

Investigations of chronic physiologic stress measured by hair cortisol are rapidly expanding among community samples of adolescents and adults. However, research examining physiologic stress among youth experiencing homelessness is nascent despite the youths’ increased risk for adverse exposures and subsequent impaired mental health.

Objective

This paper aimed to examine the feasibility of collecting hair for measuring cortisol among diverse youth experiencing homelessness and gain an understanding of variation in participation.

Methods

Analysis of survey and hair participation data from three pilot studies among youth experiencing homelessness was conducted. Survey measures included sociodemographic characteristics (age, race and ethnicity, sex assigned at birth, and sexual orientation) and reasons for nonparticipation. Descriptive analysis examined participation rates in hair collection for cortisol measurement, including sociodemographic differences in participation.

Results

Participation in the hair sampling for cortisol was high for the combined sample (88.4%), with some variation across the three pilot studies. Insufficient hair for cutting was the most common reason for not participating; Black and multiracial youth, as well as male youth, had a higher prevalence of nonparticipation.

Discussion

The collection of hair for cortisol research among youth experiencing homelessness is feasible, and integration of physiologic measures of stress into research with this vulnerable population should be considered, given their high risk for adversity and death by suicide and drug overdose. Methodologic considerations and avenues for potential research are discussed.
Clinical Characteristics of Pediatric Patients With Septic Shock Caused by Acute Appendicitis
Authors: Xie Fangnan , Wang Li , Chen Long , Li Shuanling , Shen Qiulong , Li Xianling , Liu Tingting , Chen Yongwei , Wang Dayong
Published: April 2023

Objectives

This study aimed to explore the clinical characteristics of septic shock in pediatric patients caused by acute appendicitis.

Methods

This case series included patients with septic shock caused by acute appendicitis in Beijing Children's Hospital between January 2015 and December 2020.

Results

Six patients with septic shock caused by acute appendicitis were enrolled. One patient was an infant with extremely low weight; 2 patients were obese. The diagnosis was delayed in 4 patients (the time from onset to diagnosis was 5 days in 3 children and 4 days in 1 child). All patients had abnormally raised inflammatory markers (C-reactive protein 119.17 ± 48.36 mg/L, procalcitonin 129.95 ± 86.09 ng/mL). Severe abdominal infection was found in all patients. There was appendix perforation in 4 patients and diffused peritonitis in 3 patients. Two patients had metabolic diseases (Wilson disease and decreased biotinase activity, respectively). Five patients had an appendectomy and 1 patient received conservative treatment. Five patients were discharged in stable condition, while 1 patient died.

Conclusions

Children with delayed diagnosis, abnormal body weight, significant elevation in inflammatory markers, and underlying metabolic disease may be at greater risk of complicated appendicitis and septic shock.

Evidence-Based Medicine

Level of Evidence: IV
Evaluating Multiple Magnet Ingestion at 2 Large Canadian Pediatric Hospitals After Reintroduction to the US Marketplace
Authors: Grandjean-Blanchet Charlotte , Eltorki Mohamed , Strickland Matt , Kang Ann , Wen Aaron , Rosenfield Daniel
Published: April 2023

Objectives

To determine the trend in incidence of pediatric magnet ingestions at 2 large Canadian tertiary pediatric hospitals after reintroduction of magnets to the US marketplace and to evaluate morbidity and mortality related to these ingestions.

Methods

This was a retrospective study performed in 2 tertiary care pediatric hospitals between 2004 and 2019. We reviewed the charts of all children who presented with a foreign body ingestion and included those with reported magnet ingestion. We characterized all events and compared the incidence rate before and after the US ban was overturned in 2016. Descriptive statistics were used to summarize our results. Incidence rate ratio was calculated using the total number of magnet ingestion cases and total emergency department visits normalized to 100,000 emergency department visits/year.

Results

We screened a total of 6586 ingestions and identified 192 patients with magnet ingestions. The period after the mandatory recall was compared with the period after the US ban revocation yielding an incidence rate ratio of 0.76 for all magnet ingestions (P = 0.15) and 0.73 (P = 0.34) for multiple magnet ingestions. There was, however, a graphical upward trend that immediately followed the US ban revocation. Sixty-nine patients (36%) were admitted to the hospital and 45 (23%) required a procedure to remove the magnet ingested. No deaths occurred.

Conclusions

Our findings suggest that the overturning of the US ban did not lead to a significant increase in the incidence of rare earth magnet ingestion in 2 large tertiary pediatric hospitals in Canada despite noting a trend upwards.
Imaging Evaluation for Thoracic Spine Fractures in Pediatric Trauma Patients
Authors: Ibrahim Ala , Amirabadi Afsaneh , Aquino Michael R.
Published: April 2023

Background

Imaging workup for evaluating thoracic spine fracture (TSF) in pediatric blunt trauma is variable.

Purpose

The aim of the study was to determine the number of TSFs missed by radiography and identified on computed tomography (CT) or magnetic resonance imaging (MRI) that required intervention or resulted in a change in management.

Methods

A retrospective review of children with TSFs was performed. Diagnostic images and reports for these patients were reviewed. Data regarding demographics, clinical presentation, management, and outcomes were extracted from institutional electronic medical records. Use of radiographs, CT, and MRI for evaluation of TSF was quantified. Incidence of TSFs was calculated and stratified by mechanism. The number of TSFs and complicating factors missed on radiography but identified on subsequent CT or MRI were quantified.

Results

Three thousand two hundred sixty-five trauma patients 18 years or younger were reviewed. Of these, 3.3% (90/3265) had TSFs (36 females, 54 males; mean age, 10.80 ± 4.4 years). The most common mechanism of injury was fall (43% [39/90]) followed by motor vehicle collisions (30% [27/90]). The most common fracture was simple compression fracture 64%, which occurred most frequently in the mid thoracic spine, followed by transverse process fractures 19% and spinous process fractures 7%. Almost half of all TSFs diagnosed on CT and/or MRI were missed on initial radiographs. While all fractures that required operative management were identified on radiographs, 13 of the 19 fractures that required nonoperative intervention were missed.

Conclusions

Approximately 50% of TSFs diagnosed on CT or MRI were not identified on preceding radiographs. This is similar to studies in adult populations that show poor sensitivity of radiographs.
68Ga-FAPI PET/CT Provides a Clear Picture of a Klatskin Tumor That 18F-FDG PET/CT Missed
Authors: Al-Ibraheem Akram , Al-Qasem Soud , El Khaldi Mousa , Amarin Rula
Published: April 2023

Klatskin tumor, also known as hilar cholangiocarcinoma, was clearly demonstrated in this case report by contrasting 68Ga-FAPI and 18F-FDG PET/CT in the same patient. This instance exemplifies a false-negative 18F-FDG PET/CT for the main tumor site, despite positive 68Ga-FAPI uptake at the same location.
Comparison of 18F-FDOPA and 18F-MFBG PET/CT Images of Metastatic Pheochromocytoma
Authors: Wei Feng , Wu Biao , Ling Xueying , Gong Jian , Xu Hao
Published: April 2023

A 30-year-old man with pheochromocytoma was hospitalized for hemoptysis without inducement. CT revealed a mass in the left lung, and biopsy pathology under the bronchoscope suggested that it was a pheochromocytoma metastasis. To further identify the location of the metastatic lesions, the patient was enrolled in a clinical trial and underwent 18F-FDOPA and 18F-MFBG PET/CT. Images from both examinations showed similar lesions. However, the lesions differed in that the uptake of some lesions was significantly higher with 18F-FDOPA than with 18F-MFBG, whereas the para-aortic lesion was active in 18F-MFBG but not in 18F-FDOPA.
Various Types of Facial-Angular Artery-Based Flaps for Reconstructing Oral and Maxillofacial Defects Following Cancer Ablation
Authors: Chen Wei-liang , Zhou Bin , Huang Zi-xian , Chen Rui , Dong Xiao-yu
Published: April 2023

Background:

The flap based on the facial-angular vessels (FAVs) has several names and cannot capture the hemodynamics.

Aims:

This study was performed to assess the reliability of various types of flaps based on the FAVs for reconstructing oral and maxillofacial defects following cancer ablation.

Patients and Methods:

Forty-three oral and maxillofacial defects were reconstructed with facial-angular artery island flaps (FAAIF, n=14), including V-Y advancement-type and rotation-type flaps based on FAVs and reverse-flow FAAIFs (R-FAAIF, n=29), including ipsilateral, contralateral rotation, full-thickness, and folded types, based on distal FAVs following cancer ablation. The patients (25 males and 18 females) ranged in age from 18 to 82 years. The lesions included basal cell carcinoma (n=26), squamous cell carcinoma (n=8), adenoid cystic carcinoma (n=3), mucoepidermoid carcinoma (n=3), verrucous carcinoma (n=2), and nodular melanoma (n=1). The tumors were classified as clinical stage I to III in 12, 25, and 6 cases, respectively. Lesions were observed in orbital (n=4), infraorbital (n=14), glabellar (n=2), nasal (n=4), cheek (n=10), upper lip (n=3), palate (n=4), and lower gingival (n=2) regions. The defects ranged in size from 2.0×2.5 to 5.0×12.0 cm. The skin paddle ranged in size from 1.5×3.0 to 4.0×12.0 cm.

Results:

There was 1 flap failure, resulting in a flap success rate of 97.7%. Complications, including hematoma, infection, wound dehiscence, and fistula, occurred in 15 (34.9%) patients. Limitations of mouth opening and ectropion occurred in 12 (28.0%) patients. The esthetic outcomes were satisfactory in 36 (83.7%) patients but were not significantly different between the FAAIF and R-FAAIF groups. The patients were followed up for 6 to 60 months. At the time of the last follow-up, 27 (62.8%) patients were alive with no disease, 9 (20.9%) were alive with disease, and 7 (16.3%) had died due to their disease. There was no significant survival difference between the 2 groups.

Conclusions:

Various types of FAV-based flaps are valuable reconstructive options for the treatment of oral and maxillofacial defects following clinical stage I–III cancer ablation.
Physical Therapist Management of a Person With Frailty Across the Continuum
Authors: Cabrera Jennifer
Published: April 2023

Management of the older adult with frailty is challenging. Multiple morbidities and their interrelationships can make the management of frailty arduous to diagnose and effectively treat. However, explicitly assessing for frailty can help optimize the older adult's care and provide an appropriate focus for the interventions. Effective treatment interventions must be individualized to encourage active participation and engagement. Appropriate dosing of exercise is essential. Nonetheless, the key to reversing or preventing a downward trajectory is increasing physical activity, necessitating the individual's active participation and empowerment.
Exogenous TGFβ1 and its mimic HpTGM attenuate the heart’s inflammatory response to ischaemic injury and improve long term cardiac outcomes
Authors: Redgrave Rachael E. , Singh Esha , Tual-Chalot Simon , Park Catherine , Hall Darroch , Bennaceur Karim , Smyth Danielle J. , Maizels Rick M. , Spyridopoulos Ioakim , Arthur Helen M.
Published: April 2023

Rationale

Successful and timely coronary reperfusion following acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage transiently ischaemic heart muscle. However, the subsequent inflammatory response within the infarct can lead to further loss of viable myocardium. Robust interventions are required in the acute MI setting to minimise cardiac injury and reduce risk of further detrimental progression.

Objective

TGFβ1 is an anti-inflammatory cytokine released endogenously in response to infection or tissue injury. The goal of this study was to investigate its protective effects when given exogenously following myocardial infarction.

Methods and Results

TGFβ1 is found at increased levels in the blood of STEMI patients immediately following myocardial infarction. We observe a significant correlation (p=0.003) between higher circulating TGFβ1 levels at 24h post MI and a reduction in infarct size over the following 3 months, suggesting that an early increase in circulating TGFβ1 is protective in these patients. Using a mouse model of cardiac ischaemia-reperfusion we demonstrate that additional exogenous TGFβ1 delivered in the acute setting has multiple beneficial outcomes. At 24 hours post-reperfusion It leads to a significantly smaller infarct size (30% reduction, p=0.025), reduced inflammatory infiltrate (28% reduction, p=0.015), lower intra-cardiac expression of inflammatory cytokines IL1β and CCL2 (>50 % reduction, p=0.038 and 0.0004, respectively) and reduced scar size at 4 weeks (21% reduction, p=0.015). Furthermore exogenous delivery of an equivalent dose of HpTGM, a recently described low-fibrogenic mimic of TGFβ1, secreted by a helminth parasite to evade immune rejection, has an almost identical protective effect on injured mouse hearts. Furthermore using a genetic approach we show the benefit is mediated by the vascular endothelium.

Conclusions

This work reveals the potential of exogenous TGFβ1 and HpTGM delivered in the acute MI setting to provide protective anti-inflammatory effects and reduce infarct size, leading to a smaller scar and reduced detrimental progression.
Increased activity of IRE1 improves the clinical presentation of EAE
Authors: Bracchi-Ricard Valerie , Nguyen Kayla , Ricci Daniela , Gaudette Brian , Henao-Meija Jorge , Brambilla Roberta , Martynyuk Tetyana , Gidalevitz Tali , Allman David , Bethea John R. , Argon Yair
Published: April 2023

Activation of the ER stress sensor IRE1α contributes to neuronal development and is known to induce neuronal remodelingin vitroandin vivo. On the other hand, excessive IRE1 activity is often detrimental and may contribute to neurodegeneration. To determine the consequences of increased activation of IRE1α, we used a mouse model expressing a C148S variant of IRE1α with increased and sustained activation. Surprisingly, the mutation did not affect the differentiation of highly secretory antibody-producing cells, but exhibited a strong protective effect in a mouse model of experimental autoimmune encephalomyelitis (EAE). Significant improvement in motor function was found in IRE1C148S mice with EAE relative to WT mice. Coincident with this improvement, there was reduced microgliosis in the spinal cord of IRE1C148S mice, with reduced expression of pro-inflammatory cytokine genes. This was accompanied by reduced axonal degeneration and enhanced CNPase levels, suggestiing improved myelin integrity. Interestingly, while the IRE1C148S mutation is expressed in all cells, the reduction in proinflammatory cytokines and in the activation of microglial activation marker IBA1, along with preservation of phagocytic gene expression, all point to microglia as the cell type contributing to the clinical improvement in IRE1C148S animals. Our data suggest that sustained increase in IRE1α activity can be protectivein vivo, and that this protection is cell type and context dependent. Considering the overwhelming but conflicting evidence for the role of the ER stress in neurological diseases, a better understanding of the function of ER stress sensors in physiological contexts is clearly needed.
Arabidopsis thalianasubclass I ACTIN DEPOLYMERIZING FACTORs regulate nuclear organization and gene expression
Authors: Matsumoto Tomoko , Higaki Takumi , Takatsuka Hirotomo , Kutsuna Natsumaro , Ogata Yoshiyuki , Hasezawa Seiichiro , Umeda Masaaki , Inada Noriko
Published: April 2023

ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein that regulates the organization and dynamics of actin microfilaments. Eleven ADFs in theArabidopsis thalianagenome are grouped into four subclasses, and subclass I ADFs, ADF1–4, are all expressed throughout the plant. Previously, we showed that subclass I ADFs function in the regulation of the response against powdery mildew fungus as well as in the regulation of cell size and endoreplication. Here, we report a new role of subclass I ADFs in the regulation of nuclear organization and gene expression. Through a microscopic observation of epidermal cells in mature leaves, we found that the size of chromocenters in bothadf4and transgenic lines where expression of subclass IADFs are downregulated (ADF1-4Ri) was reduced compared with that of wild-type Col-0.A. thalianapossesses eightACTINgenes, among whichACT2,-7, and-8are expressed in vegetative organs. The chromocenter size inact7, but not in theact2/8double mutant, was enlarged compared with that in Col-0. Microarray analysis revealed that 1,818 genes were differentially expressed inadf4andADF1-4Ri. In particular, expression of 22 nucleotide-binding leucine-rich repeat (NLR) genes, which are involved in effector-triggered plant immunity, was reduced inadf4andADF1-4Ri. qRT-PCR confirmed the altered expressions shown with microarray analysis. Overall, these results suggest that ADF regulates various aspects of plant physiology through its role in regulation of nuclear organization and gene expression. The mechanism how ADF and ACTIN regulate nuclear organization and gene expression is discussed.
Structural rather than catalytic role for mitochondrial respiratory chain supercomplexes
Authors: Brischigliaro Michele , Cabrera-Orefice Alfredo , Arnold Susanne , Viscomi Carlo , Zeviani Massimo , Fernández-Vizarra Erika
Published: April 2023

Mammalian mitochondrial respiratory chain (MRC) complexes are able to associate into quaternary structures named supercomplexes (SCs), which normally coexist with non bound individual complexes. The functional significance of SCs has not been fully clarified and the debate has been centered on whether or not they confer catalytic advantages to the non-bound individual complexes. Mitochondrial respiratory chain organization does not seem to be conserved in all organisms. In fact, and differently from mammalian species, mitochondria fromDrosophila melanogastertissues are characterized by low amounts of SCs, despite the high metabolic demands and MRC activity shown by these mitochondria. Here, we show that attenuating the biogenesis of individual respiratory chain complexes was accompanied by increased formation of stable SCs, which are missing inDrosophila melanogasterin physiological conditions. This phenomenon was not accompanied by an increase in mitochondrial respiratory activity. Therefore, we conclude that SC formation is necessary to stabilize the complexes in suboptimal biogenetic conditions, but not for the enhancement of respiratory chain catalysis.
Validation of polymorphic Gompertzian model of cancer throughin vitroandin vivodata
Authors: Soboleva Arina , Kaznatcheev Artem , Cavill Rachel , Schneider Katharina , Staňková Kateřina
Published: April 2023

Mathematical modeling plays an important role in our understanding and targeting therapy resistance mechanisms in cancer. The polymorphic Gompertzian model, analyzed theoretically by Viossat and Noble, describes a heterogeneous cancer population consisting of therapy sensitive and resistant cells. This theoretically promising model has not previously been validated with real-world data. In this study, we provide this validation. We demonstrate that the polymorphic Gompertzian model successfully captures trends in bothin vitroandin vivodata on non-small cell lung cancer (NSCLC) dynamics under treatment. Additionally, for thein vivodata of tumor dynamics in patients undergoing treatment, we compare the polymorphic Gompertzian model to the classical oncologic models, which were previously identified as the models that fit this data best. We show that the polymorphic Gompertzian model can successfully capture the U-shape trend in tumor size during cancer relapse, which can not be fitted with the classical oncologic models. In general, the polymorphic Gompertzian model corresponds well to bothin vitroandin vivoreal-world data, suggesting it as a candidate for improving the efficacy of cancer therapy, for example through evolutionary/adaptive therapies.
Peanut Shell Carbon Nanocellulose Preparation, Analysis and Plausible Role in Regenerative Medicine Using Mesenchymal Stem Cell Line C3H10t1/2
Authors: Kannupriya  , Bhatia Yeshika , Rai Seemha , Mahajan Nidhi
Published: April 2023

Peanut Shell is a major agro industry waste. Cellulose, the most abundant crystalline component of naturally porous peanut shell biomass. Nanomaterial science has actively used peanut shell as a source of nanocellulose. However, there are few reports on the biocompatibility of cellulose nanocrystal based nanocomposites from agro on mesenchymal cell lines. To evaluate how mesenchymal stem cells behave onto this scaffold in vitro, cellulose nanocrystals (CNCs) made from peanut shells were combined with polyvinyl alcohol (PVA) to create tissue engineering scaffolds. SEM images illustrated that for PVA/CNC nanocomposites and clean PVA respectively, increasing the CNC concentration was accompanied with pore size enlargement. The nanocomposite’s three-dimensional porous structure conveyed uneven and intertwined pore structures in additionto the pore distribution. The highest relative crystallinity was observed at 10 wt% of CNCs, according to X-ray diffraction, which also showed that the relative crystallinity of the PVA with 0 and 5 wt% of CNCs was lower than that of neat PVA. In order to confirm the modifications in chemical functional groups, Fourier transform infrared spectroscopy was utilized. The non-cytotoxicity of PVA/CNC_10% was measured for cell viability during an in vitro cytotoxicity test. Additionally, the acquired PVA/biocompatibility CNC’s with the Murine Mesenchymal cell line (C 3H 10T 1/2) demonstrated good cell spreading and adherence to the material surfaces. These results suggest that future research into the in vitro integration of mesenchymal cells with a PVA/CNC scaffold can prove to be a promising candidate for regenerative purposes.
Energetic driving force for LHCII clustering in plant membranes
Authors: Manna Premashis , Hoffmann Madeline , Davies Thomas , Richardson Katherine H. , Johnson Matthew P. , Schlau-Cohen Gabriela S.
Published: April 2023

Plants protect themselves against photodamage from excess energy using a process known as non-photochemical quenching (NPQ). A significant fraction of NPQ is induced by a ΔpH across the membrane, which changes the conformation, composition, and organization of the antenna complexes. In particular, clustering of the major light-harvesting complex (LHCII) has been observed, yet the thermodynamic driving force behind this reorganization has not been determined, largely because measurements of membrane protein interaction energies have not been possible. Here, we introduce a method to quantify membrane protein interaction energies and its application to the thermodynamics of LHCII clusters. By combining single-molecule measurements of LHCII-proteoliposomes at different protein densities and a rigorous analysis of LHCII clusters and photophysics, we quantified the LHCII-LHCII interaction energy to be approximately -5kBTat neutral pH and at least -7kBTat acidic pH. From these values, we found the thermodynamic driving force for LHCII clustering was dominated by these enthalpic contributions. Collectively, this work captures the membrane protein-protein interactions responsible for LHCII clustering from the perspective of equilibrium statistical thermodynamics, which has a long and rich tradition in biology.
Bijections between the multifurcating unlabeled rooted trees and the positive integers
Authors: Maranca Alessandra Rister Portinari , Rosenberg Noah A.
Published: April 2023

Abstract

Colijn and Plazzotta (Systematic Biology67:113-126, 2018) described a bijective scheme for associating the unlabeled bifurcating rooted trees with the positive integers. In mathematical and biological applications of unlabeled rooted trees, however, nodes of rooted trees are sometimes multifurcating rather than bifurcating. Building on the bijection between the unlabeled bifurcating rooted trees and the positive integers, we describe bijective schemes for associating the unlabeledmultifurcatingrooted trees with the positive integers. We devise bijections with the positive integers for a set of trees in which each non-leaf node hasexactly kchild nodes, and for a set of trees in which each non-leaf node hasat most kchild nodes. The calculations make use of Macaulay’s binomial expansion formula. The generalization to multifurcating trees can assist with the use of unlabeled trees for applications in evolutionary biology, such as the measurement of phylogenetic patterns of genetic lineages in pathogens.

Mathematics subject classification (2020)

05C05, 05C30, 92D15
Data-driven prediction of colonization outcomes for complex microbial communities
Authors: Wu Lu , Wang Xu-Wen , Tao Zining , Wang Tong , Zuo Wenlong , Zeng Yu , Liu Yang-Yu , Dai Lei
Published: April 2023

Complex microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse physical, biochemical, and ecological processes governing microbial dynamics. Here, we proposed a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validated this approach using synthetic data, finding that machine learning models (including Random Forest and neural ODE) can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conducted colonization experiments for two commensal gut bacteria speciesEnterococcus faeciumandAkkermansia muciniphilain hundreds of human stool-derivedin vitromicrobial communities, confirming that the data-driven approach can successfully predict the colonization outcomes. Furthermore, we found that while most resident species were predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., the presence ofEnterococcus faecalisinhibits the invasion ofE. faecium. The presented results suggest that the data-driven approach is a powerful tool to inform the ecology and management of complex microbial communities.
Previous breeding success and carrion substrate together influence subsequent carrion choice by adultNicrophorus vespilloides
Authors: Park Hyun Woo , Issar Swastika , Kilner Rebecca M.
Published: April 2023

Insects can adjust their behaviour in relation to experience in a wide range of contexts including foraging, mate selection, and choice of oviposition site. Here we investigate whether burying beetles modulate their choice of carrion in relation to the outcome of their past breeding experience. Burying beetles require small vertebrate carrion to reproduce. Beetle parents convert carrion into an edible nursery for their larvae, whom they typically care for throughout larval development. We tested whether a beetle’s past breeding experience influenced its subsequent choice of carrion, when presented simultaneously with either a dead mouse or a dead chick. We found that both male and female beetles favoured the same carrion as used in their first breeding attempt – but only if they had produced many larvae and only if they had previously bred on a mouse. Beetles that had produced fewer larvae on a dead mouse switched to favouring dead chicks in their second breeding attempt. Those that had bred on a dead chick chose carrion at random subsequently, regardless of their previous breeding success. Our general conclusion is that burying beetles can integrate different sources of information about their past breeding experience with current cues when selecting carrion for reproduction.
Comparison of three quantitative approaches for estimating time-since-deposition from autofluorescence and morphological profiles of cell populations from forensic biological samples
Authors: Gentry Amanda Elswick , Ingram Sarah , Philpott M. Katherine , Archer Kellie J. , Ehrhardt Christopher J.
Published: April 2023

Determining when DNA recovered from a crime scene transferred from its biological source, i.e., a sample’s ‘time-since-deposition’ (TSD), can provide critical context for biological evidence. Yet, there remains no analytical techniques for TSD that are validated for forensic casework. In this study, we investigate whether morphological and autofluorescence measurements of forensically-relevant cell populations generated with Imaging Flow Cytometry (IFC) can be used to predict the TSD of ‘touch’ or trace biological samples. To this end, three different prediction frameworks for estimating the number of day(s) for TSD were evaluated: the elastic net, gradient boosting machines (GBM), and generalized linear mixed model (GLMM) LASSO. Additionally, we transformed these continuous predictions into a series of binary classifiers to evaluate the potential utility for forensic casework. Results showed that GBM and GLMM-LASSO showed the highest accuracy, with mean absolute error estimates in a hold-out test set of 29 and 21 days, respectively. Binary classifiers for these models correctly binned 94-96% and 98-99% of the age estimates as over/under 7 or 180 days, respectively. This suggests that predicted TSD using IFC measurements coupled to one or, possibly, a combination binary classification decision rules, may provide probative information for trace biological samples encountered during forensic casework.
GSR-DB: a manually curated and optimised taxonomical database for 16S rRNA amplicon analysis
Authors: Molano Leidy-Alejandra G. , Vega-Abellaneda Sara , Manichanh Chaysavanh
Published: April 2023

Amplicon-based 16S ribosomal RNA sequencing remains the most widely used method to profile microbial communities, as a low-cost and low-complexity approach. Reference databases are a mainstay for taxonomic assignments, which typically rely on popular databases such as SILVA, Greengenes, GTDB, or RDP. However, the inconsistency of the nomenclature across databases, and the presence of shortcomings in the annotation of these databases are limiting the resolution of the analysis. To overcome these limitations, we created the GSR database (Greengenes, SILVA, and RDP database), an integrated and manually curated database for bacterial and archaeal 16S amplicon taxonomy analysis. Unlike previous integration approaches, this database creation pipeline includes a taxonomy unification step to ensure consistency in taxonomical annotations. The database was validated with three mock communities and two real datasets and compared with existing 16S databases such as Greengenes, GTDB, ITGDB, SILVA, RDP, and MetaSquare. Results showed that the GSR database enhances taxonomical annotations of 16S sequences, outperforming current 16S databases at the species level. The GSR database is available for full-length 16S sequences and the most commonly used hypervariable regions: V4, V1-V3, V3-V4, and V3-V5.

IMPORTANCE

Taxonomic assignments of microorganisms have long been hindered by inconsistent nomenclature and annotation issues in existing databases like SILVA, Greengenes, GTDB, or RDP. To overcome these issues, we created GSR-DB, accurate and comprehensive taxonomic annotations of 16S amplicon data. Unlike previous approaches, our innovative pipeline includes a unique taxonomy unification step, ensuring consistent and reliable annotations. Validated with mock communities and real datasets, GSR-DB outperforms existing databases in providing species-level resolution, making it a game-changer for microbiome studies. Moreover, GSR-DB is designed to be accessible to researchers with limited computational resources, making it a powerful tool for scientists across the board. Available for full-length 16S sequences and commonly used hypervariable regions, including V4, V1-V3, V3-V4, and V3-V5, GSR-DB is a go-to database for robust and accurate microbial taxonomy analysis.
Annotating Metagenomically Assembled Bacteriophage from a Unique Ecological System using Protein Structure Prediction and Structure Homology Search
Authors: Say Henry , Joris Ben , Giguere Daniel , Gloor Gregory B.
Published: April 2023

Emergent long read sequencing technologies such as Oxford’s Nanopore platform are invaluable in constructing high quality and complete genomes from a metagenome, and are needed investigate unique ecosystems on a genetic level. However, generating informative functional annotations from sequences which are highly divergent to existing nucleotide and protein sequence databases is a major challenge. In this study, we present wet and dry lab techniques which allowed us to generate 5432 high quality sub-genomic sized metagenomic circular contigs from 10 samples of microbial communities. This unique ecological system exists in an environment enriched with naphthenic acid (NA), which is a major toxic byproduct in crude oil refining and the major carbon source to this community. Annotation by sequence homology alone was insufficient to characterize the community, so as proof of principle we took a subset of 227 putative bacteriophage and greatly improved our existing annotations by predicting the structures of hypothetical proteins with ColabFold and using structural homology searching with Foldseek. The proportion of proteins for each bacteriophage that were highly similar to known proteins increased from approximately 10% to about 50%, while the number of annotations with KEGG or GO terms increased from essentially 0% to 15%. Therefore, protein structure prediction and homology searches can produce more informative annotations for microbes in unique ecological systems. The characterization of novel microbial ecosystems involved in the bioremediation of crude oil-process-affected wastewater can be greatly improved and this method opens the door to the discovery of novel NA degrading pathways.

IMPORTANCE

Functional annotation of metagenomic assembled sequences from novel or unique microbial communities is challenging when the sequences are highly dissimilar to organisms or proteins in the known databases. This is a major obstacle for researchers attempting to characterize the functional capabilities of unique ecosystems. In this study, we demonstrate that including protein structure prediction and homology search based methods vastly improves the annotation of predicted genes identified in novel putative bacteriophage in a bacterial community that degrades naphthenic acids the major toxic component of oil refinery wastewater. This method can be extended to similar genomics studies of unique, uncharacterized ecosystems, to improve their annotations.

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Heat stress impairs centromere structure and segregation of meiotic chromosomes in Arabidopsis
Authors: Khaitova Lucie Crhak , Mikulkova Pavlina , Pecinkova Jana , Kalidass Manikandan , Heckmann Stefan , Lermontova Inna , Riha Karel
Published: April 2023

Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis inArabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres inArabidopsisare highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.