bluuebunny/crossref_metadata_2025 huggingface dataset:
#6746 SAFETY OF ANGIOTENSIN RECEPTOR-NEPRILISIN INHIBITOR IN PERITONEAL DIALYSIS PATIENTS WITH HEART FAILURE: A MULTI-CENTER COHORT STUDY
Authors: Pimenta Gonçalo , Afonso Rita , Vida Ana Carlota , Gomes Daniel , Maltes Sergio , Matias Patrícia , Duraes José , Aguiar Carlos , Silva Gil , Branco Patricia , Calça Ana Rita
Published: June 2023

Background and Aims

Sacubitril/valsartan, the first approved angiotensin receptor neprilisin inhibitor (ARNi), is the current cornerstone in the treatment of heart failure with reduced ejection fraction (HFrEF), reducing hospitalizations and mortality. However, in patients with chronic kidney disease stage 5D, who have the highest prevalence of congestive heart failure, its use is still not approved. The aim of this study was to evaluate the safety of sacubitril/valsartan in peritoneal dialysis (PD) patients with HFrEF.

Method

Multi-center cross-sectional cohort study including 5 PD patients with NYHA class II-IV HFrEF who started sacubitril/valsartan between 2017 and 2022. Demographic and clinical data were collected from the electronic records. Clinical, biochemical and echocardiographic parameters were compared before and after treatment initiation.

Results

A total of 5 patients (all male) were included with a mean age of 71±9 years and a median follow-up time of 16 months (IQR 22). The dose of sacubitril/valsartan was 24/26mg, 2 times per day in all patients. The indication to start PD was hypervolemia in all patients and the mean left ventricular ejection fraction at PD beginning was 35±8%. DPCA was the modality of choice in all patients and 4 were under icodextrin. All patients had coronary artery disease and 3 patients were obese and diabetic. All patients were taking furosemide and 4 patients were under a beta-blocker and a SGLT-2 inhibitor. During follow-up, left ventricular ejection fraction increased from 35±8% to 38±8% (P = .018) and median residual diuresis decreased 25 mL per month (IQR 66), but none of the patients became anuric. De novo hyperkalemia or hypotension did not develop in any of the patients. No significant difference in blood pressure profile was noticed. A major adverse cardiovascular event occurred in only one patient (myocardial infarction requiring coronary artery revascularization and hospitalization). No deaths were reported.

Conclusion

Our results suggest that ARNi can be used safely in patients under PD with major cardiovascular risk. Further randomized studies are warranted to confirm safety and clarify the benefit of this therapy in PD patients with HFrEF.
#6833 ARE KT RECIPIENTS TAKING THEIR IMMUNOSUPPRESSANT MEDICATION? PRELIMINARY EVIDENCE FROM A SUPER-SPECIALIZED TRANSPLANT CENTRE IN SUB-SAHARAN AFRICA
Authors: Olatise Olalekan , Muoka Michael , Asaolu Stephen , Adekoya Adebowale , Olatise Adaku , Faponle Adegboyega
Published: June 2023

Background and Aims

Immunosuppressant non-adherence is a leading cause of preventable renal allograft dysfunction, rejection and graft loss. The barriers to immunosuppressant adherence as well as associated risk factors of non-adherence vary across studies in different locations. This study aimed to investigate the prevalence of immunosuppressant non-adherence among adult kidney transplant recipients and identify barriers to adherence in a renal transplant cohort.

Method

A cross sectional survey was conducted using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), the Immunosuppressant Therapy Barrier Scale and the Beliefs about Medicines Questionnaire. Adherence was defined according to the BAASIS, with barriers to adherence and beliefs about medicines compared between the two groups. Participants were recruited from the out-patient clinic at Zenith Medical and Kidney centre. An advert for the study was placed in consultation rooms and patients were approached to join the study when they attend appointments. IBM SPSS Statistics for Windows, Version 23 (Armonk, NY: IBM Corp) was used for data analysis.

Results

The rate of non-adherence was 50.7% out of 67 kidney transplant recipients attending outpatient clinic. There were statistically significant associations between non-adherence and occupation (P = 0.049). Participants who are on MMF were more adherent than those on sirolimus (97.0% vs 79.4% and 0.0% vs 8.8%) and this difference is statistically significant (P = .038). Also, participants who have had one or more post-transplant hospital admission are more non-adherent when compared with those that have never been admitted (P = .022) The only significant barrier to adherence was when patients travelled out of town (P < 0.005). Adherence was not associated with patients’ belief about their medicines.

Conclusion

Interventions aimed at ensuring constant access to immunosuppressant drugs and those based on habit forming may significantly improve adherence in this cohort.
#6921 INFECTIOUS PERITONITIS DURING PEDIATRIC PERITONEAL DIALYSIS
Authors: Abdellatif Abir , Jellouli Manel , Bousetta Abir , Sayari Taha , Gader Ameni , Gargah Tahar
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) is the dialysis treatment modality of choice used to treat pediatric patients with end-stage kidney disease (ESKD), thanks to its various benefits. However, infectious complications, mainly infectious peritonitis (IP), can occur, leading to morbidity, mortality and technique's failure. In this study, we aimed to describe the deferent infectious complications observed in children on PD and to investigate the risk factors for the occurrence of IP.

Method

In this study, we retrospectively collected the records of 99 patients who were treated with PD within the last eleven years (2010-2020) in the department of pediatrics of the University Hospital Charles Nicolle in Tunis. We adopted the terminology of the International Society of Peritoneal Dialysis (ISPD) to define peritonitis and its outcome. Analysis examining possible predictive factors of IP were performed using parametric and non-parametric tests and multivariate logistic regression in multivariate analysis.

Results

Ninety-nine patients were on PD during our study period, of which 65 patients had a total of 120 episodes of IP. The incidence of IP was 0.41 episodes per patient/year. The average time to onset of the first episode of IP was 1.2 years [3 days – 5.54 years]. Clinical signs of IP were dominated by abdominal pain (78.3%) and fever (50.4%). The PD effluent was cloudy in 78.3% of cases. Peritoneal dialysis fluid culture was positive in 33.3% of episodes with a predominance of gram-positive germs (62.8%). The evolution of this IP was favourable in 91.5% of cases with a response to antibiotics. 7% of episodes were relapsing of which five were during the first episode of IP. IP recurrence occurred in one patient. A catheter change was required over 16 episodes of IP, and hemodialysis sessions were necessary in 27 patients, temporary in 10 patients. The multivariate study identified the following predictive factors of IP: poor adherence to treatment (OR=3.851; 95%CI: 1.369-10.837; P = .011) and weight less than 15 Kg (OR=6.314; 95%CI: 1.333- 29.897; P = .02).

Conclusion

Considering the high risk of peritonitis in children on PD, it is imperative to establish a primary prevention based on training of the child's caregivers and families. Continous quality improvement program and PD technique must systematically reviewed in every peritonitis episode. Nutritional management of children prior to the start of PD is necessary to limit the risk of IP.
#6929 SGLT2 INHIBITORS IN IGA NEPHROPATHY: REAL LIFE EXPERIENCE AT OUR CENTRE
Authors: Carvalho Renata , Medeiros Joana , Pires Olga , Bastos José Mário , Ribeiro Bárbara , Viana Johanna Rodrigues , Vaz Raquel , Marques Sofia Homem Melo
Published: June 2023

Background and Aims

SGLT2 inhibitors (SGLT2i) have a beneficial effect in diabetic and non-diabetic proteinuric chronic kidney disease (CKD), demonstrated in large randomized controlled trials. However, there is limited information about real life experience with SGLT2i in non-diabetic CKD like IgA nephropathy (IgAN).

Method

All patients with biopsy-proven IgA nephropathy since 2015 were evaluated for SGLT2i use. We collected data on age, gender, the use of renin-angiotension-aldosterone system inhibitors (RAASi), eGFR, glycosuria and proteinuria at baseline, at 6 months and at one year of follow-up. Glomerular filtration rate (eGFR) was estimated using the CKD-EPI equation. Data was analyzed using Jamovi®.

Results

51 patients had IgAN diagnosed by kidney biopsy from April 2015 until March 2021. Eleven of these started SGLT2i between December 2020 and February 2022 (at their physician's description). Their median age was 52, nine were male and all were taking RAASi. The initial median proteinuria was 1 g/g (range 0.5-2.0 g/g), median eGFR was 57.5 mL/min (range 16.8-104 mL/min). At 6 months, the median proteinuria was 0.7 g/g (range 0.8-4.8 g/g), median eGFR was 42.6 mL/min (range 13.9-108 mL/min). One year after beginning SGLT2i, 8 patients have laboratory values and the median value of proteinuria was 0.85 g/g (range 0.2-3.0 g/g) and the median eGFR was 40.5 mL/min (range 14.5-85.4 mL/min). All patients had glycosuria at all urine evaluations confirming no discontinuations of the SGLT2i. No serious adverse events were reported and none of the patients needed dialysis or died. There were no significant differences between proteinuria and eGFR between evaluations at the start, 6 months and 1 year of follow-up.

Conclusion

SGLT2i have become important drugs in IgAN. Our first cases who started SGLT2i showed good compliance (using glycosuria as an indirect tool to monitor adherence) and no adverse events, irrespective of their initial eGFR. The small sample was probably a limitation to the lack of significant results.
It’s me again… Ask avoidance and the dynamics of charitable giving
Authors: Späth Maximilian
Published: June 2023

Charities typically ask potential donors repeatedly for a donation. These repeated requests might trigger avoidance behaviour. Considering that, this article analyses the impact of offering the option to opt-out of receiving future fundraising asks on charitable giving. In a proposed utility framework, any opt-out option decreases the social pressure to donate. At the same time, an unconditional opt-out option induces feelings of gratitude toward the fundraiser, which may lead to a reciprocal increase in donations. The results of a lab experiment designed to disentangle the two channels show no negative impact of the option to avoid repeated asking for donations. Instead, the full model indicates a positive impact of the reciprocity channel. This finding suggests that it might be beneficial for charities to introduce an unconditional opt-out option during high-frequency fundraising campaigns.
Racial Disparities in MiT Family Translocation Renal Cell Carcinoma
Authors: Lu Xiaofan , Tawanaie Pour Sedehi Nassim , Su Xiaoping , Yan Fangrong , Alhalabi Omar , Tannir Nizar M , Malouf Gabriel G
Published: June 2023

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian (2 of 14 [14.3%] vs 10 of 525 [1.9%]; P = .036) and Black (8 of 113 [7.1%] vs 1.9%; P = .007) patients with RCC showed significantly higher prevalence of TRCC compared with White patients with RCC. The overall mortality rate of TRCC was slightly higher in Asian and Black patients compared with White patients (HR: 6.05, P = .069). OrigiMed2020 Chinese patients with RCC had a significantly higher proportion of TRCC with TFE3 fusions than TCGA White patients with RCC (13 of 250 [5.2%] vs 7 of 525 [1.3%]; P = .003). Black patients with TRCC were more likely to exhibit the proliferative subtype than White patients (6 of 8 [75%] vs 2 of 9 [22.2%]; P = .057) for those who had RNA-seq profiles. We present evidence of higher prevalence of TRCC in Asian and Black patients with RCC compared with White patients and show that these tumors in Asian and Black patients have distinct transcriptional signatures and are associated with poor outcomes.
The Quebec Dental Anomalies Registry: Identifying genes for rare disorders
Authors: Wredenhagen Madeleine S , Goldstein Andee , Mathieu Hélène , Miranda Valancy , Morali Burcin , Santerre Jacinthe , Maftei Catalina , Delrue Marie-Ange , Schmittbuhl Matthieu , Vu Duy Dat , Moldovan Florina , Campeau Philippe M
Published: June 2023

There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.
Structural and functional differences in the brains of patients with MCI with and without depressive symptoms and their relations with Alzheimer's disease: an MRI study
Authors: Chiari-Correia Rodolfo Dias , Tumas Vitor , Santos Antônio Carlos , Salmon Carlos Ernesto G
Published: June 2023

Background

The mild cognitive impairment (MCI) stage among elderly individuals is very complex, and the level of diagnostic accuracy is far from ideal. Some studies have tried to improve the 'MCI due to Alzheimer's disease (AD)' classification by further stratifying these patients into subgroups. Depression-related symptoms may play an important role in helping to better define the MCI stage in elderly individuals.

Objective

In this work, we explored functional and structural differences in the brains of patients with nondepressed MCI (nDMCI) and patients with MCI with depressive symptoms (DMCI), and we examined how these groups relate to AD atrophy patterns and cognitive functioning.

Methods

Sixty-five participants underwent MRI exams and were divided into four groups: cognitively normal, nDMCI, DMCI, and AD. We compared the regional brain volumes, cortical thickness, and white matter microstructure measures using diffusion tensor imaging among groups. Additionally, we evaluated changes in functional connectivity using fMRI data.

Results

In comparison to the nDMCI group, the DMCI patients had more pronounced atrophy in the hippocampus and amygdala. Additionally, DMCI patients had asymmetric damage in the limbic-frontal white matter connection. Furthermore, two medial posterior regions, the isthmus of cingulate gyrus and especially the lingual gyrus, had high importance in the structural and functional differentiation between the two groups.

Conclusion

It is possible to differentiate nDMCI from DMCI patients using MRI techniques, which may contribute to a better characterization of subtypes of the MCI stage.
Shakespeare’s Metaphysical Poem: Allegory, Metaphysics, and Aesthetics in ‘The Phoenix and Turtle’
Authors: Tregear Ted
Published: June 2023

Long treated as a poetic curio or a biographical riddle, Shakespeare’s poetic contribution to the 1601 Loves Martyr—usually known as ‘The Phoenix and Turtle’—has recently been reclaimed as an experiment in metaphysical poetry. This essay sets out to ask what that means: for the poem, for metaphysical poetry, and for metaphysics itself. It argues that Shakespeare draws on the language of metaphysics, and its canonical problems, to test the relationship between poetic and philosophical thinking. It follows the poem as it charts the efforts, and failures, of both allegory and metaphysics to apprehend the thought-defying love between phoenix and turtle. It shows how that love engages the dilemma of the particular and the universal, a dilemma native to metaphysics since Aristotle, but felt most acutely in the realm of aesthetic experience. And it suggests that, in sounding out the limits of metaphysical reason, Shakespeare’s poem allows for poetry to think in a way that metaphysics cannot. ‘The Phoenix and Turtle’ ends in mourning: for the death of phoenix and turtle, and for the demise of the metaphysical transcendentals they seemed in hindsight to uphold. That mourning might nonetheless offer poetry its vocation, as the space where reason might remember and reflect on the object of its loss.
A true caudal fin or not? New insights in the evolution of the gadiform caudal fin
Authors: Moritz Timo , Walter Jacqueline , Grunow Bianka , Thieme Philipp
Published: June 2023

The distinctive caudal-fin skeleton of gadiforms has puzzled scientists for a long time, because of its many differences in comparison to other teleosts. Contradicting hypotheses interpreted this structure as (i) a highly derived teleostean caudal fin, (ii) a new formation with parts from the caudal, dorsal and anal fins, a so called pseudocaudal, or (iii) a complete evolutionary novelty, a so called neocaudal. To shed light on to this issue, the caudal-fin ontogeny of Lota lota was studied in detail. It differs from the development in non-gadiform teleostean taxa, e.g. by absence of a distinct and early notochord flexion. However, there are also many similarities with other teleosts, e.g. the caudal fin develops before the dorsal and anal fins. Furthermore, the morphology of adult caudal fins of all major gadiform families were studied and reviewed. Our results, in combination with the latest molecular phylogenies, allowed us to discuss the evolution of the gadiform caudal fin and resolve the origin of this highly debated character complex. Although their caudal-fin skeleton shows several derived apomorphies, the gadiform caudal fin is homologous to the caudal fins of other teleosts, without principal inclusion of dorsal- or anal-fin elements.
TATA-box-binding protein promotes hepatocellular carcinoma metastasis through epithelial-mesenchymal transition
Authors: Cao Jiayi , Yang Suzhen , Luo Tingting , Yang Rui , Zhu Hanlong , Zhao Tianming , Jiang Kang , Xu Bing , Wang Yingchun , Chen Fulin
Published: June 2023

Background:

HCC characterizes malignant metastasis with high incidence and recurrence. Thus, it is pivotal to discover the mechanisms of HCC metastasis. TATA-box-binding protein (TBP), a general transcriptional factor (TF), couples with activators and chromatin remodelers to sustain the transcriptional activity of target genes. Here, we investigate the key role of TBP in HCC metastasis.

Methods:

TBP expression was measured by PCR, western blot, and immunohistochemistry. RNA-sequencing was performed to identify downstream proteins. Functional assays of TBP and downstream targets were identified in HCC cell lines and xenograft models. Luciferase reporter and chromatin immunoprecipitation assays were used to demonstrate the mechanism mediated by TBP.

Results:

HCC patients showed high expression of TBP, which correlated with poor prognosis. Upregulation of TBP increased HCC metastasis in vivo and in vitro, and muscleblind-like-3 (MBNL3) was the effective factor of TBP, positively related to TBP expression. Mechanically, TBP transactivated and enhanced MBNL3 expression to stimulate exon inclusion of lncRNA-paxillin (PXN)-alternative splicing (AS1) and, thus, activated epithelial-mesenchymal transition for HCC progression through upregulation of PXN.

Conclusions:

Our data revealed that TBP upregulation is an HCC enhancer mechanism that increases PXN expression to drive epithelial-mesenchymal transition.
Race differences in pain and pain-related risk factors among former professional American-style football players
Authors: Edwards Robert R. , Tan Can Ozan , Dairi Inana , Whittington Alicia J. , Thomas Julius Dewayne , Campbell Claudia M. , Ross Edgar , Taylor Herman A. , Weisskopf Marc , Baggish Aaron L. , Zafonte Ross , Grashow Rachel
Published: June 2023

The burden of pain is unequal across demographic groups, with broad and persisting race differences in pain-related outcomes in the United States. Members of racial and ethnic minorities frequently report more pervasive and severe pain compared with those in the majority, with at least some disparity attributable to differences in socioeconomic status. Whether race disparities in pain-related health outcomes exist among former professional football players is unknown. We examined the association of race with pain outcomes among 3995 former professional American-style football players who self-identified as either Black or White. Black players reported more intense pain and higher levels of pain interference relative to White players, even after controlling for age, football history, comorbidities, and psychosocial factors. Race moderated associations between several biopsychosocial factors and pain; higher body mass index was associated with more pain among White but not among Black players. Fatigue and psychosocial factors were more strongly related to pain among Black players relative to White players. Collectively, the substantial social and economic advantages of working as a professional athlete did not seem to erase race-related disparities in pain. We highlight an increased burden of pain among elite Black professional football players and identify race-specific patterns of association between pain and biopsychosocial pain risk factors. These findings illuminate potential future targets of interventions that may serve to reduce persistent disparities in the experience and impact of pain.
The evasive truth: do mere exposures at the subliminal and supraliminal levels drive the illusory truth effect?
Authors: Sasaki Kyoshiro , Kobayashi Maiko , Nakamura Koyo , Watanabe Katsumi
Published: June 2023

The subjective truth of a statement is boosted by mere exposure to itself or a part of itself. This phenomenon is referred to as the
illusory truth effect
. We examined whether subliminal pre-exposure to the statement topic would increase its subjective truth. In the exposure phase, participants observed the topic, which was presented supraliminally or subliminally. After the exposure phase, they rated the subjective truth of the statement. If unconscious processing contributed to the illusory truth effect, subliminal exposure to the topic would increase the subjective truth of the statement. On the other hand, if the illusory truth effect required conscious and controlled processing, increases in the subjective truth of a statement would be induced only by supraliminal exposure to the topic. The results showed that the illusory truth effect was not found in either supraliminal or subliminal groups. Our findings provide no reliable evidence that pre-exposure to the statement topic saliently promotes its subjective truth.
Entropic uncertainty relations from equiangular tight frames and their applications
Authors: Rastegin Alexey E.
Published: June 2023

Finite tight frames are interesting in various topics including questions of quantum information. Each complex tight frame leads to a resolution of the identity in the Hilbert space. Symmetric informationally complete measurements are a special class of equiangular tight frames. Applications of such frames in quantum physics deserve more attention than they have obtained. We derive uncertainty relations for a quantum measurement assigned to an equiangular tight frame. Main results follow from estimation of the corresponding index of coincidence. State-dependent and state-independent formulations are both addressed. Also, we discuss applications of considered measurements to detect entanglement and other correlations.
Ecological factors drive the divergence of morphological, colour and behavioural traits in cactus wrens (Aves, Troglodytidae)
Authors: Andrade-González Violeta Monserrath , Vázquez-Miranda Hernán , Ornelas-García Claudia Patricia , Sosa-López José Roberto
Published: June 2023

The study of ecological mechanisms influencing organisms' phenotypic variation is a central subject of evolutionary biology. In this study, we characterized morphological, plumage colour and acoustic variation in cactus wrensCampylorhynchus brunneicapillusthroughout its distribution. We assessed whether Gloger's, Allen's and Bergmann's ecogeographical rules, and the acoustic adaptation hypothesis relate to geographical trait variation. We analysed specimen coloration in belly and crown plumage, beak shape and structural song characteristics. We tested whether the subspecific classification or the peninsular/mainland groups mirrored the geographical variation in phenotypes and whether ecological factors were associated with patterns of trait variation. Our results suggest that colour, beak shape and acoustic traits varied across the range, in agreement with two lineages described by genetics. The simple versions of Gloger's and Allen's rules are related to variations in colour traits and morphology. Conversely, patterns of phenotypic variation did not support Bergmann's rule. The acoustic adaptation hypothesis supported song divergence for frequency-related traits. Phenotypic variation supports the hypothesis of two taxa:C. affinisin the Baja California peninsula andC. brunneicapillusin the mainland. The ecological factors are associated with phenotypic trait adaptations, suggesting that divergence between lineages could result from ecological divergence.
A giant armoured skink from Australia expands lizard morphospace and the scope of the Pleistocene extinctions
Authors: Thorn Kailah M. , Fusco Diana A. , Hutchinson Mark N. , Gardner Michael G. , Clayton Jessica L. , Prideaux Gavin J. , Lee Michael S. Y.
Published: June 2023

There are more species of lizards and snakes (squamates) alive today than any other order of land vertebrates, yet their fossil record has been poorly documented compared with other groups. Here, we describe a gigantic Pleistocene skink from Australia based on extensive material that includes much of the skull and postcranial skeleton, and spans ontogenetic stages from neonate to adult.
Tiliqua frangens
substantially expands the known ecomorphological diversity of squamates. At approximately 2.4 kg, it was more than double the mass of any living skink, with an exceptionally broad, deep skull, squat limbs and heavy, ornamented body armour. It probably filled the armoured herbivore niche that land tortoises (testudinids), absent from Australia, occupy on other continents.
Tiliqua frangens
and other giant Plio-Pleistocene skinks suggest that small-bodied groups that dominate vertebrate biodiversity might have lost their largest and often most morphologically extreme representatives in the Late Pleistocene, expanding the scope of these extinctions.
Developmental and functional controls on enrolment in an ancient, extinct arthropod
Authors: Esteve Jorge , Hughes Nigel C.
Published: June 2023

Three-dimensional models reveal how the mechanics of exoskeletal enrolment changed during the development of a model organism for insights into ancient arthropod development, the 429-million-year-old trilobiteAulacopleura koninckii.Changes in the number, size and allocation of segments within the trunk, coupled with the need to maintain effective exoskeletal shielding of soft tissue during enrolment, necessitated a transition in enrolment style about the onset of mature growth. During an earlier growth phase, enrolment was sphaeroidal, with the venter of the trunk fitting exactly against that of the head. In later growth, if lateral exoskeletal encapsulation was to be maintained trunk length proportions did not permit such exact fitting, requiring an alternative, non-sphaeoridal enrolment style. Our study favours the adoption of a posture in later growth in which the posterior trunk extended beyond the front of the head. This change in enrolment accommodated a pattern of notable variation in the number of mature trunk segments, well known to characterize the development of this species. It suggests how an animal whose early segmental development was remarkably precisely controlled was able to realize the marked variation in mature segment number that was related, apparently, to life in a physically challenging, reduced oxygen setting.
A new dolphin with tusk-like teeth from the late Oligocene of New Zealand indicates evolution of novel feeding strategies
Authors: Coste Ambre , Fordyce R. Ewan , Loch Carolina
Published: June 2023

All extant toothed whales (Cetacea, Odontoceti) are aquatic mammals with homodont dentitions. Fossil evidence from the late Oligocene suggests a greater diversity of tooth forms among odontocetes, including heterodont species with a variety of tooth shapes and orientations. A new fossil dolphin from the late Oligocene of New Zealand,Nihohae matakoigen. et sp. nov., consisting of a near complete skull, earbones, dentition and some postcranial material, represents this diverse dentition. Several preserved teeth are horizontally procumbent, including all incisors and canines. These tusk-like teeth suggest adaptive advantages for horizontally procumbent teeth in basal dolphins. Phylogenetic analysis placesNihohaeamong the poorly constrained basal waipatiid group, many with similarly procumbent teeth. Features ofN. matakoisuch as its dorsoventrally flattened and long rostrum, long mandibular symphysis, unfused cervical vertebrae, lack of attritional or occlusal wear on the teeth and thin enamel cover suggest the rostrum and horizontally procumbent teeth were used to injure and stun prey though swift lateral head movements, a feeding mode that did not persist in extant odontocetes.
Nasopharyngeal Staphylococcus aureus colonization among HIV-infected children in Addis Ababa, Ethiopia: Antimicrobial susceptibility pattern and association with Streptococcus pneumoniae colonization
Authors: Gebre Henok Alemu , Wami Ashenafi Alemu , Kebede Eyerusalem Solomon , Yidnekachew Melaku , Gebre Meseret , Negash Abel Abera
Published: June 2023

Background

Staphylococcus aureus and Streptococcus pneumoniae are common inhabitants of the nasopharynx of children. HIV-infected children have higher risk of invasive diseases caused by these pathogens. With widespread use of pneumococcal conjugate vaccines and the emergence of methicillin-resistant S aureus, the interaction between S. aureus and S. pneumoniae is of a particular significance. We sought to determine the magnitude of colonization by methicillin-sensitive and -resistant S. aureus and colonization by S. pneumoniae; associated risk factors and antimicrobial susceptibility pattern among HIV-Infected children in Addis Ababa, Ethiopia.

Method

A prospective observational study was conducted in 183 HIV-infected children at ALERT hospital Addis Ababa, Ethiopia from September 2016 to August 2018. S. aureus and S. pneumoniae were identified using standard bacteriological techniques, antimicrobial susceptibility testing was performed on S. aureus and screening for methicillin resistance was carried out by amplifying the mecA gene. Risk factors were analyzed by using binary logistic regression.

Results

The prevalence of nasopharyngeal S. aureus, MRSA and S. pneumoniae colonization were 27.3%, 2.7% and 43.2% respectively. Multivariable analysis indicated an inverse association between S. aureus and S. pneumoniae nasopharyngeal colonization (aOR, 0.49; CI, (0.24, 0.99); p= 0.046). The highest level of resistance in both methicillin sensitive S. aureus (MSSA) and MRSA was observed against tetracycline.

Conclusions

We found an inverse association between S. aureus and S. pneumoniae colonization among HIV-infected children. Continued assessment of the impact of pneumococcal conjugate vaccines and anti-retroviral therapy on nasopharyngeal bacterial ecology is warranted.
In-vitro assessment of Thyme oil (Thymus vulgaris) as antifungal agent against Phyllosticta citricarpa
Authors: Magunga Bheki Thapelo , Malebo Ntsoaki Joyce
Published: June 2023

Abstract: The spread of Citrus black spot (CBS) is a major concern in the citrus industry because the disease threatens fruit marketability and citrus tree health. Furthermore, there is a public concern about the safety and side effects of synthetic fungicides currently being used to control citrus black spot. Synthetic fungicides are reported to have carcinogenic effects on humans and are also toxic to the environment, however this depends on the structure of the active ingredient and the dose present. Furthermore, microorganisms tend to develop resistance to most synthetic fungicides. This problem has prompted research into the identification of new ways with broad activity in treatment of microbial disease in plants such as the use of essential oils.
The purpose of the study was to investigate the use of Thyme oil (Thymus vulgaris) as an alternative antifungal against Citrus Black Spot (CBS). Thyme oil was characterised using GC/MS. Thymol (32.1%) and ρ-Cymene (20.4%), were identified, as major compounds. Furthermore, the minimum inhibitory concentration (MIC) of essential oils against the test organism was 25 (µg/ml). The antifungal activity of Thyme oil, Thyme hydrosol and antifungal anti-mitochondrials was tested in vitro against Phyllosticta citricarpa using the agar diffusion bioassay. Comparative antifungal activity was observed between antifungal anti-mitochondrial, Thyme oil and hydrosol as indicated by an inhibition zone, minimal growth and maximum growth zone towards the edge of the plate. We propose that Thyme oil, like antifungal anti-mitochondrials, inhibits fungal growth by targeting structures with increased mitochondrial activity. This was further confirmed by Scanning Electron Microscopy (SEM) and XTT colorimetric assay. This indicates that Thyme oil and hydrosol can be used as potential alternative antifungal agents against Citrus Black Spot (CBS).
Occurrence and prevalence of bacteria from door handles at the University of Port Harcourt Teaching Hospital and its multi-drug resistance implication
Authors: Edi Deinmo , Ejiohuo Ovinuchi , Ordinioha Best
Published: June 2023

Background: The COVID-19 pandemic has heightened concerns regarding transmitting hospital-acquired infections through high contact points in healthcare facilities, such as door handles, which can serve as reservoirs for pathogenic microorganisms. With the increased infectivity of the SARS-CoV-2 virus, there is a greater risk of multidrug-resistant bacteria on these surfaces, necessitating strict surveillance prevention protocols.
Objective: This study assesses the occurrence and prevalence of bacteria on toilet door handles at the University of Port Harcourt Teaching Hospital in Nigeria and its multi-drug resistant implication. We examined the hospital infection level and overall sanitary condition.
Method: Assessment of experimental data from our study on hospital door knobs in different locations. Eighty-six samples were collected from toilet door handles at the University of Port Harcourt Teaching Hospital. Ethical approval was obtained from the hospital departments and the university research ethics committee. Samples from private offices and doors without handles were excluded. Bacteria were isolated from the samples, and antibiotic sensitivity testing was performed.
Result: Of the 329 bacteria isolated, 55.5% are Gram-positive and 44.4% Gram-negative. The most prevalent bacteria are Staphylococcus epidermidis, followed by Bacillus sp. The prevalence of multidrug-resistant bacteria was also low, with Enterococcus sp. having the highest prevalence of 28.57%, followed by Micrococcus sp. at 3.45% and Staphylococcus epidermidis at 1.96%.
Conclusion: The results show that despite the occurrence of pathogenic microorganisms, there is a reduction in the prevalence of multidrug-resistant bacteria strains. This study can be used as an environmental microbiological surveillance in suspected outbreak investigations, checking sanitary conditions and the prevalence of multidrug-resistant bacteria in healthcare facilities.
TidyTron: Reducing lab waste using validated wash-and-reuse protocols for common plasticware in Opentrons OT-2 lab robots
Authors: Bryant John A. , Longmire Cameron , Sridhar Sriya , Janousek Samuel , Kellinger Mason , Wright R. Clay
Published: June 2023

Every year biotechnology labs generate a combined total of ∼5.5 million tons of plastic waste. As the global bioeconomy expands, biofoundries will inevitably increase plastic consumption in-step with synthetic biology scaling. Decontamination and reuse of single-use plastics could increase sustainability and reduce recurring costs of biological research. However, throughput and variable cleaning quality make manual decontamination impractical in most instances. Automating single-use plastic cleaning with liquid handling robots makes decontamination more practical by offering higher throughput and consistent cleaning quality. However, open-source, validated protocols using low-cost lab robotics for effective decontamination of plasticware—facilitating safe reuse—have not yet been developed. Here we introduce and validate TidyTron: a library of protocols for cleaning micropipette tips and microtiter plates that are contaminated with DNA,E. coli, andS. cerevisiae. We tested a variety of cleaning solutions, contact times, and agitation methods with the aim of minimizing time and cost, while maximizing cleaning stringency and sustainability. We tested and validated these cleaning procedures by comparing fresh versus cleaned tips and plates for contamination with cells, DNA, or cleaning solutions. We assessed contamination by measuring colony forming units by plating, PCR efficiency and DNA concentration by qPCR, and event counts and debris by flow cytometry. Open source cleaning protocols are available athttps://github.com/PlantSynBioLab/TidyTronand hosted on a graphical user interface athttps://jbryantvt.github.io/TidyTron/.
New T2T assembly ofCryptosporidium parvumIOWA annotated with reference genome gene identifiers
Authors: de Paula Baptista Rodrigo , Xiao Rui , Li Yiran , Glenn Travis C. , Kissinger Jessica C.
Published: June 2023

Cryptosporidium parvumis a significant pathogen causing gastrointestinal infections in humans and animals, that is spread through the ingestion of contaminated food and water. Despite its global impact on public health, generating aC. parvumgenome sequence has always been challenging due to a lack ofin vitrocultivation systems and challenging sub-telomeric gene families. A gapless telomere to telomere genome assembly has been created forCryptosporidium parvumIOWA obtained from Bunch Grass Farms, named here as CpBGF. There are 8 chromosomes that total 9,259,183 bp. The new hybrid assembly which was generated with Illumina and Oxford Nanopore resolves complex sub-telomeric regions of chromosomes 1, 7 and 8. To facilitate ease of use and consistency with the literature, whenever possible, chromosomes have been oriented and genes in this annotation have been given the same gene IDs used in the current reference genome sequence generated in 2004. The annotation of this assembly utilized considerable RNA expression evidence, thus, untranslated regions, long noncoding RNAs and antisense RNAs are annotated. The CpBGF genome assembly serves as a valuable resource for understanding the biology, pathogenesis, and transmission ofC. parvum, and it facilitates the development of diagnostics, drugs, and vaccines against cryptosporidiosis.
Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis
Authors: Ackermann Tobias , Shokry Engy , Deshmukh Ruhi , Anand Jayanthi , Galbraith Laura C.A. , Mitchell Louise , Rodriguez-Blanco Giovanny , Villar Victor H. , Sterken Britt Amber , Nixon Colin , Zanivan Sara , Blyth Karen , Sumpton David , Tardito Saverio
Published: June 2023

The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density. We found that secretion of the anti-ferroptotic factors, identified as monounsaturated fatty acid (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depends on the low expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of Sec-tRNAsec biosynthesis, an essential step for selenoprotein production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells that are no longer protected by the MUFA-rich environment of the primary tumour.
A constitutive model for the remodelling erythrocyte membrane skeleton during the active invasion by the malaria merozoite
Authors: Msosa Chimwemwe , Abdalrahman Tamer , Franz Thomas
Published: June 2023

Malaria merozoites phosphorylate erythrocyte membrane proteins to breach the membrane during invasion. This study aimed to develop a constitutive model for erythrocyte membrane phosphorylation that reduces the membrane’s elastic modulus and resistance to merozoite invasion. The hyperelastic Mooney Rivlin constitutive model was adapted by adding an exponential term to represent the mechanical effect of erythrocyte membrane phosphorylation. The modified algorithm was verified with the unmodified Mooney Rivlin model for the intact erythrocyte membrane and used to predict erythrocyte membrane stress for equi-biaxial membrane strain up to 1.1 for different severity of phosphorylation damage. The stability of the damage model was assessed using the Drucker criterion for equi-biaxial strain up to 2.0. Strain and stress predicted with the developed damage model and the Mooney Rivlin model agreed for the intact erythrocyte membrane. The membrane stress at a strain of 1.1 decreased by 42% for minor and 95% for severe erythrocyte membrane damage. The stability strain threshold of the damage model was 1.98 for minor and 1.19 for severe membrane damage. The developed model can represent different degrees of erythrocyte membrane damage through phosphorylation by a malaria merozoite. The model will enablein silicoinvestigations of the invasiveness of malaria merozoites.
Synthetic gene circuits combining CRISPR interference and CRISPR activation inE. coli: importance of equal guide RNA binding affinities to avoid context-dependent effects
Authors: Barbier Içvara , Kusumawardhani Hadiastri , Chauhan Lakshya , Harlapur Pradyumna Vinod , Jolly Mohit Kumar , Schaerli Yolanda
Published: June 2023

Gene expression control based on CRISPR has emerged as a powerful approach for constructing synthetic gene circuits. While the use of CRISPR interference (CRISPRi) is already well-established in prokaryotic circuits, CRISPR activation (CRISPRa) is less mature and combination of the two in the same circuits is only just emerging. Here, we report that combining CRISPRi with SoxS-based CRISPRa inEscherichia colican lead to context-dependent effects due to different affinities in the formation of CRISPRa and CRISPRi complexes, resulting in loss of predictable behaviour. We show that this effect can be avoided by using the same scaffold guide RNA structure for both complexes.
Alternative splicing is coupled to gene expression in a subset of variably expressed genes
Authors: Karlebach Guy , Steinhaus Robin , Danis Daniel , Devoucoux Maeva , Anczuków Olga , Sheynkman Gloria , Seelow Dominik , Robinson Peter N
Published: June 2023

Numerous factors regulate alternative splicing of human genes at a co-transcriptional level. However, how alternative splicing depends on the regulation of gene expression is poorly understood. We leveraged data from the Genotype-Tissue Expression (GTEx) project to show a significant association of gene expression and splicing for 6874 (4.9%) of 141,043 exons in 1106 (13.3%) of 8314 genes with substantially variable expression in ten GTEx tissues. About half of these exons demonstrate higher inclusion with higher gene expression, and half demonstrate higher exclusion, with the observed direction of coupling being highly consistent across different tissues and in external datasets. The exons differ with respect to sequence characteristics, enriched sequence motifs, RNA polymerase II binding, and inferred transcription rate of downstream introns. The exons were enriched for hundreds of isoform-specific Gene Ontology annotations, suggesting that the coupling of expression and alternative splicing described here may provide an important gene regulatory mechanism that might be used in a variety of biological contexts. In particular, higher inclusion exons could play an important role during cell division.
Predicting the placement of biomolecular structures on AFM substrates based on electrostatic interactions
Authors: Amyot Romain , Kodera Noriyuki , Flechsig Holger
Published: June 2023

Atomic force microscopy (AFM) and high-speed AFM allow direct observation of biomolecular structures and their functional dynamics. Based on scanning the molecular surface of a sample deposited on a supporting substrate by a probing tip, topographic images of its dynamic shape are obtained. Critical to successful AFM observations is a balance between immobilization of the sample while avoiding too strong perturbations of its functional conformational dynamics. Since the sample placement on the supporting substrate cannot be directly controlled in experiments, the relative orientation isa prioriunknown, and, due to limitations in the spatial resolution of images, difficult to infer froma posteriorianalysis. We present a method to predict the macromolecular placement of samples based on electrostatic interactions with the AFM substrate and demonstrate applications to HS-AFM observations of the Cas9 endonuclease, an aptamer-protein complex, and the ClpB molecular chaperone. The model also allows predictions of imaging stability under tip-scanning. We implemented the developed method within the freely available BioAFMviewer software package. Therefore, predictions based on available structural data can be made even prior to an actual experiment.