bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferring With TACT
Authors: Armstrong Alexandra , Engstrand Shannon , Kunz Sarah , Cole Alexandra , Schenkel Sara , Kucharski Keri , Toole Cheryl , DeGrazia Michele
Published: September 2022

Background:

Neonatal patients who no longer require level IV neonatal intensive care unit care are transferred to less acute levels of care. Standardized assessment tools have been shown to be beneficial in the transfer of patient care. However, no standardized tools were available to assist neonatal providers in the assessment and communication of the infants needs at transfer.

Purpose:

The purpose was to develop a Transfer Assessment and Communication Tool (TACT) that guides provider decision making in the transfer of infants from a level IV neonatal intensive care unit to a less acute level of care within a regionalized healthcare system.

Methods:

Phase 1 included developing the first draft of the TACT using retrospective data, known variables from published literature, and study team expertise. In phase 2, the final draft of the TACT was created through feedback from expert neonatal providers in the regionalized care system using e-Delphi methodology.

Results:

The first draft of the TACT, developed in phase 1, included 36 characteristics. In phase 2, nurses, nurse practitioners, and physician experts representing all levels of newborn care participated in 4 e-Delphi surveys to develop the final draft of the TACT, which included 74 weighted characteristics.

Implications for Practice and Research:

Potential benefits of the TACT include improved communication across healthcare teams, reduced risk for readmission, and increased caregiver visitation. The next steps are to validate the TACT for use either retrospectively or in real time, including characteristic weights, before implementation of this tool in the clinical setting.
Be Sweet to Babies
Authors: Bujalka Helena , Cruz Melinda , Ingate Vivien , Cheong Jeanie , Duffy Natalie , Eeles Abbey , Spence Kaye , Spittle Alicia , Sweet Linda , Saracino Amy Tagliante , Harrison Denise
Published: September 2022

Background:

Evidence for analgesic effects of parent-led pain management strategies during painful procedures in newborn infants exists; however, such strategies are inconsistently used in practice. A publicly available parent-targeted video demonstrates breastfeeding, skin-to-skin care, and sucrose during painful procedures. Australian parents' use and knowledge of this video and these strategies was unknown.

Purpose:

To determine parents' use of pain management strategies, and perceived acceptability and usefulness of the parent-targeted video.

Methods:

A cross-sectional, online, anonymous survey with embedded video. Participants were recruited via social media channels of the Miracle Babies Foundation, an Australian parent support network. Target participants were parents or family members of infants currently or previously hospitalized in neonatal special and/or intensive care nurseries, or high dependency units.

Results:

A total of 162 of 189 respondents provided sufficient data for analysis; all identified as mothers. Only 6 (4%) had previously seen the video; however, nearly all rated it as potentially useful and helpful (n = 124, 82%). Although most reported that sucrose had been used (n = 112, 84%), fewer reported having used skin-to-skin care (n = 50, 37%), or breastfeeding (n = 33, 25%). Most intended to advocate for skin-to-skin care (n = 108, 88%) or breastfeeding (n = 100, 81%) in future procedures. Perceived barriers to utilizing strategies included lack of information-sharing and organizational practices that excluded parent involvement.

Implications for Practice and Research:

The video may be valuable in supporting mothers to advocate for their involvement during painful procedures in preterm and sick hospitalized infants. Further research is recommended to explore coordinated strategies targeting parents and healthcare professionals to overcome barriers to implementing parent-led infant pain management strategies.
Impact of diet on hydrogen sulfide production: implications for gut health
Authors: Teigen Levi , Biruete Annabel , Khoruts Alexander
Published: September 2022

Purpose of review

Excessive hydrogen sulfide (H2S) production by the gut microbiota may contribute to the pathogenesis of multiple intestinal diseases, including colon cancer and ulcerative colitis. Therefore, understanding of dietary drivers of H2S production has potential implications for nutritional strategies to optimize gut health and treat intestinal diseases.

Recent findings

Recent studies support a positive relationship between dietary protein intake and H2S production. However, protein rarely exists in isolation in the diet, and dietary fiber intake could reduce H2S production in humans and animals, even with ∼30% of calories derived from protein.

These findings suggest that increased fiber intake may reduce H2S production irrespective of protein intake, enabling the ability to meet the metabolic demands of the illness while supporting gut health. Here we discuss two recent ulcerative colitis diet studies that illustrate this point.
Hyperspectral Imaging Allows Evaluation of Free Flaps in Craniomaxillofacial Reconstruction
Authors: Thoenissen Philipp , Heselich Anja , Al-Maawi Sarah , Sader Robert , Ghanaati Shahram
Published: September 2022

Introduction:

Treatment of extended defects after tumor resection in oral, maxillofacial, and facial surgery (craniomaxillofacial) is usually performed by free microvascular flaps. Evaluation of flap survival is crucial, especially in the first hours after insertion and connection. For flap evaluation various invasive and noninvasive methods have been developed. This retrospective clinical study examined the ability of a hyperspectral imaging (HSI) camera (Tivita, Diaspective Vision, Germany) to assess postoperative flap properties in comparison to established clinical parameters.

Materials and Methods:

Thirteen patients with tumor resection and free flap reconstruction were included for camera analysis and another 10 patients as control group. For this purpose, at defined time intervals and under standardized conditions, recordings of transplants 3 to 100 hours postoperatively were performed. Images were used to examine oxygenation (StO2%), tissue hemoglobin index, tissue water index, near infrared range perfusion index of free flaps quantitatively and qualitatively.

Results:

HSI provides values differing between patients observed with no intraindividual significant difference. After 24 hours a mean reduction of 16.77% for StO2%, 9.16% for tissue hemoglobin index and 8.46% was observed, going in line with no loss of flap was noted in the observation period.

Conclusion:

HSI is suitable as a noninvasive measure for the evaluation of free flaps in craniomaxillofacial surgery in case of stable imaging conditions with respect to light, surrounding and position of the camera. However, clinical measurements are still the method of choice.
A Predictive Model for Chronic Hydrocephalus After Clipping Aneurysmal Subarachnoid Hemorrhage
Authors: Zhang Feng , Cai Xian-Feng , Zhao Wei , Wang Yu-Hai , He Jian-Qing
Published: September 2022

Chronic hydrocephalus after clipping aneurysmal subarachnoid hemorrhage (aSAH) often results in poor outcomes. This study was to establish and validate model to predict chronic hydrocephalus after aSAH by least absolute shrinkage and selection operator logistic regression. The model was constructed from a retrospectively analyzed. Two hundred forty-eight patients of aSAH were analyzed retrospectively in our hospital from January 2019 to December 2021, and the patients were divided into chronic hydrocephalus (CH) group (n=55) and non-CH group (n=193) according to whether occurred CH within 3 months. In summary, 16 candidate risk factors related to chronic hydrocephalus after aSAH were analyzed. Univariate analysis was performed to judging the risk factors for CH. The least absolute shrinkage and selection operator regression was used to filter risk factors. Subsequently, the nomogram was designed by the above variables. And area under the curve and calibration chart were used to detect the discrimination and goodness of fit of the nomogram, respectively. Finally, decision curve analysis was constructed to assess the practicability of the risk of chronic hydrocephalus by calculating the net benefits. Univariate analysis showed that age (60 y or older), aneurysm location, modified Fisher grade, Hunt-Hess grade, and the method for cerebrospinal fluid drainage, intracranial infections, and decompressive craniectomy were significantly related to CH (P<0.05). Whereas 5 variables [age (60 y or older), posterior aneurysm, modified Fisher grade, Hunt-Hess grade, decompression craniectomy] from 16 candidate factors were filtered by LASSO logistic regression for further research. Area under the curve of this model was 0.892 (95% confidence interval: 0.799–0.981), indicating a good discrimination ability. Meanwhile, the result of calibration indicated a good fitting between the prediction probability and the actual probability. Finally, decision curve analysis showed a good clinical efficacy. In summary, this model could conveniently predict the occurrence of chronic hydrocephalus after aSAH. Meanwhile, it could help physicians to develop personalized treatment and close follow-up for these patients.
Beyond Total Mesorectal Excision
Authors: Stelzner Sigmar , Heinze Tillmann , Heimke Marvin , Gockel Ines , Kittner Thomas , Brown Gina , Mees Sören T. , Wedel Thilo
Published: September 2022

Objective:

Magnetic resonance imaging–based subdivision of the pelvis into 7 compartments has been proposed for pelvic exenteration. The aim of the present anatomical study was to describe the topographic anatomy of these compartments and define relevant landmarks and surgical dissection planes.

Background:

Pelvic anatomy as it relates to exenterative surgery is complex. Demonstration of the topographic peculiarities of the pelvis based on the operative situs is hindered by the inaccessibility of the small pelvis and the tumor bulk itself.

Materials and Methods:

Thirteen formalin-fixed pelvic specimens were meticulously dissected according to predefined pelvic compartments. Pelvic exenteration was simulated and illustrated in a stepwise manner. Different access routes were used for optimal demonstration of the regions of interest.

Results:

All the 7 compartments (peritoneal reflection, anterior above peritoneal reflection, anterior below peritoneal reflection, central, posterior, lateral, inferior) were investigated systematically. The topography of the pelvic fasciae and ligaments; vessels and nerves of the bladder, prostate, uterus, and vagina; the internal iliac artery and vein; the course of the ureter, somatic (obturator nerve, sacral plexus), and autonomic pelvic nerves (inferior hypogastric plexus); pelvic sidewall and floor, ischioanal fossa; and relevant structures for sacrectomy were demonstrated.

Conclusions:

A systematic approach to pelvic anatomy according to the 7 magnetic resonance imaging–defined compartments clearly revealed crucial anatomical landmarks and key structures facilitating pelvic exenterative surgery. Compartment-based pelvic anatomy proved to be a sound concept for beyond TME surgery and provides a basis for tailored resection procedures.
ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth
Authors: Zhai Yuqi , Chan Wai Wa Ray , Li Wen , Lau Kwok-Fai
Published: September 2022

ADP-ribosylation factor 6 (ARF6) is a small GTPase that has a variety of neuronal functions including stimulating neurite outgrowth, a crucial process for the establishment and maintenance of neural connectivity. As impaired and atrophic neurites are often observed in various brain injuries and neurological diseases, understanding the intrinsic pathways that stimulate neurite outgrowth may provide insights into developing strategies to trigger the reconnection of injured neurons. The neuronal adaptor FE65 has been shown to interact with ARF6 and potentiate ARF6-mediated neurite outgrowth. However, the precise mechanism that FE65 activates ARF6 remains unclear, as FE65 does not possess a guanine nucleotide exchange factor (GEF) domain/function. Here, we show that FE65 interacts with the ARF6 GEF, namely the ARF nucleotide-binding site opener (ARNO). Moreover, a complex consisting of ARNO, ARF6 and FE65 is detected. Notably, FE65 potentiates the stimulatory effect of ARNO on ARF6-mediated neurite outgrowth, and the effect of FE65 is abrogated by an FE65 mutation that disrupts FE65–ARNO interaction. Additionally, the intramolecular interaction for mediating the autoinhibited conformation of ARNO is attenuated by FE65. Moreover, FE65 potentiates the effects of wild-type ARNO, but not the monomeric mutant, suggesting an association between FE65 and ARNO dimerization. Collectively, we demonstrate that FE65 binds to and activates ARNO and, consequently, potentiates ARF6-mediated neurite outgrowth.
Familial ALS-associated
SFPQ
variants promote the formation of SFPQ cytoplasmic aggregates in primary neurons
Authors: Widagdo Jocelyn , Udagedara Saumya , Bhembre Nishita , Tan Jing Zhi Anson , Neureiter Lara , Huang Jie , Anggono Victor , Lee Mihwa
Published: September 2022

Splicing factor proline- and glutamine-rich (SFPQ) is a nuclear RNA-binding protein that is involved in a wide range of physiological processes including neuronal development and homeostasis. However, the mislocalization and cytoplasmic aggregation of SFPQ are associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). We have previously reported that zinc mediates SFPQ polymerization and promotes the formation of cytoplasmic aggregates in neurons. Here we characterize two familial ALS (fALS)-associated
SFPQ
variants, which cause amino acid substitutions in the proximity of the SFPQ zinc-coordinating centre (N533H and L534I). Both mutants display increased zinc-binding affinities, which can be explained by the presence of a second zinc-binding site revealed by the 1.83 Å crystal structure of the human SFPQ L534I mutant. Overexpression of these fALS-associated mutants significantly increases the number of SFPQ cytoplasmic aggregates in primary neurons. Although they do not affect the density of dendritic spines, the presence of SFPQ cytoplasmic aggregates causes a marked reduction in the levels of the GluA1, but not the GluA2 subunit of AMPA-type glutamate receptors on the neuronal surface. Taken together, our data demonstrate that fALS-associated mutations enhance the propensity of SFPQ to bind zinc and form aggregates, leading to the dysregulation of AMPA receptor subunit composition, which may contribute to neuronal dysfunction in ALS.
Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents
Authors: Viera Carlos R. , Stevens Bradley T. , Viera Talysa , Zielinski Cameron , Uranga Lee A. , Rogelj Snezna , Patidar Praveen L. , Tello-Aburto Rodolfo
Published: September 2022

A series of cystargolide-based β-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz portion of the cystargolide scaffold is well tolerated, producing analogues with low nanomolar proteasome inhibition activity, in many cases superior to carfilzomib. Additionally, analogue
8g
, containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC
50
= 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.
Identification of promising anti-EBOV inhibitors:de novodrug design, molecular docking and molecular dynamics studies
Authors: Mohamed Eslam A. R. , Abdelwahab Sayed F. , Alqaisi Ahmad M. , Nasr Amaal Mohammed Salih , Hassan Heba Ali
Published: September 2022

The Ebola virus (EBOV) outbreak was recorded as the largest in history and caused many fatalities. As seen in previous studies, drug repurposing and database filtration were the two major pathways to searching for potent compounds against EBOV. In this study, a deep learning (DL) approach via the LigDream tool was employed to obtain novel and effective anti-EBOV inhibitors. Based on the galidesivir (BCX4430) chemical structure, 100 compounds were collected and inspected using variousin silicoapproaches. Results from the molecular docking study indicated that mol1_069 and mol1_092 were the best two potent compounds with a docking score of −7.1 kcal mol−1and −7.0 kcal mol−1, respectively. Molecular dynamics simulations, in addition to binding energy calculations, were conducted over 100 ns. Both compounds exhibited lower binding energies than BCX4430. Furthermore, compared with BCX4430 (%Absorption = 60.6%), mol1_069 and mol1_092 scored higher values of % Absorption equal to 68.1% and 63.7%, respectively. The current data point to the importance of using DL in the drug design process instead of conventional methods such as drug repurposing or database filtration. In conclusion, mol1_069 and mol1_092 are promising anti-EBOV drug candidates that require furtherin vitroandin vivoinvestigations.
Facile preparation of Fe
3
O
4
@Pt nanoparticles as peroxidase mimics for sensitive glucose detection by a paper-based colorimetric assay
Authors: He Ye , Wang Panlin , Chen Xiaojing , Li Yahuang , Wei Jiajun , Cai Guoxi , Aoyagi Kiyoshi , Wang Wenxiang
Published: September 2022

A simple strategy to rapidly detect glucose was developed by utilizing core (Fe
3
O
4
)–shell (Pt) magnetic nanoparticles (Fe
3
O
4
@Pt NPs) as a nanoenzyme and a paper-based colorimetric sensor. In the presence of H
2
O
2
, Fe
3
O
4
@Pt NPs catalyze the redox reaction of 3,3′,5,5′-tetramethylbenzidine (TMB) and generate a colour change from colourless to blue. On this basis, a colorimetric glucose sensing method assisted by glucose oxidase (GOx) was developed. Under the optimal conditions, the detection limits of the proposed assay for H
2
O
2
and glucose were 0.36 µM and 1.27 µM, respectively. Furthermore, the fabricated colorimetric method was successfully applied to analyze glucose concentrations by using a paper device as a measuring platform without a spectrometer. In addition, this method exhibited satisfactory recovery for glucose detection in human serum samples and urine samples, which satisfied the requirements for normal detection of real samples. This study provides a good candidate for health monitoring of glucose and also expands the applications of nanoenzymes and paper-based colorimetric assays in point-of-care testing.
Communication and action predictability: two complementary strategies for successful cooperation
Authors: Woźniak Mateusz , Knoblich Guenther
Published: September 2022

Making one's actions predictable and communicating what one intends to do are two strategies to achieve interpersonal coordination. It is less clear whether these two strategies are mutually exclusive or whether they can be used in parallel. Here, we asked how the availability of communication channels affects the use of strategy to make one's actions predictable. In three experiments, we investigated how people reach joint decisions if they are not allowed to communicate at all (Experiment 1), allowed minimal reciprocal communication (Experiment 2), or allowed to use the full range of conventional communication (Experiment 3). We found that when participants were not allowed to communicate, coordination was achieved by increasing action predictability. When conventional communication was allowed, there were no attempts to increase action predictability. In the minimal reciprocal communication condition, successful pairs both increased action predictability and established a communication system. Overall, this study demonstrates that people are able to flexibly adapt to coordination challenges during joint decision making and that communication reduces behavioural constraints on joint action coordination.
Flexibility in the social structure of male chimpanzees (
Pan troglodytes schweinfurthii
) in the Budongo Forest, Uganda
Authors: Badihi Gal , Bodden Kelsey , Zuberbühler Klaus , Samuni Liran , Hobaiter Catherine
Published: September 2022

Individuals of social species experience competitive costs and social benefits of group living. Substantial flexibility in humans' social structure and the combination of different types of social structure with fission–fusion dynamics allow us to live in extremely large groups—overcoming some of the costs of group living while capitalizing on the benefits. Non-human species also show a range of social strategies to deal with this trade-off. Chimpanzees are an archetypical fission–fusion species, using dynamic changes in day-to-day association to moderate the costs of within-group competition. Using 4 years of association data from two neighbouring communities of East African chimpanzees (
Pan troglodytes schweinfurthii
), we describe an unexplored level of flexibility in chimpanzee social structure. We show that males from the larger Waibira community (
N
= 24–31) exhibited additional structural levels of semi-stable core–periphery society, while males from the smaller Sonso community (
N
= 10–13) did not. This novel core–periphery pattern adds to previous results describing alternative modular social structure in other large communities of chimpanzees. Our data support the hypothesis that chimpanzees can incorporate a range of strategies in addition to fission–fusion to overcome costs of social living, and that their social structures may be closer to that of modern humans than previously described.
Developmental risk sensitivity theory: the effects of socio-economic status on children's risky gain and loss decisions
Authors: Harvey Teresa , Blake Peter R.
Published: September 2022

Evolutionary developmental theories propose that early environments shape human risk preferences. Developmental risk sensitivity theory (D-RST) focuses on the plasticity of risk preferences during childhood and makes predictions about the effect of reward size based on a child's social environment. By contrast, prospect theory predicts risk aversion for gains and risk seeking for losses regardless of environment or status. We presented 4 to 10-year-olds (n= 194) with a set of trials in which they chose between a certain amount and a chance to receive more or nothing. Two trials were equal expected value choices that differed by stake size and two were unequal expected value choices. Children either received gain trials or loss trials. Social environment was assessed using socio-economic status (SES) and subjective social status. Results confirmed the predictions of D-RST for gains based on SES. Children from lower-SES families differentiated between the high- and low-value trials and made more risky decisions for the high-value reward compared with higher-SES children. Children from higher-SES families were more risk averse for both trial types. Decisions for loss trials did not conform completely to either theory. We discuss the results in relation to evolutionary developmental theories.
Trunk control in and out of an episode of recurrent low back pain during the Balance-Dexterity Task
Authors: Shih Hai-Jung Steffi , Ai Joyce , Abe Justin , Tang Jiaxi , Rowley K. Michael , Van Dillen Linda R. , Kulig Kornelia
Published: September 2022

We investigated motor control strategies utilized by individuals with recurrent low back pain (rLBP) during active pain and remission periods as well as by back-healthy controls using the Balance-Dexterity Task. Nineteen young adults with rLBP were tested first when they were in pain and then again in symptom remission, and 19 matched controls were also tested. Trunk kinematic coupling and muscle co-activation were examined while participants performed the task by standing on one leg while compressing a spring with a maximum consistent force with the other leg. We found a decreased bilateral external oblique co-activation and a further reduced trunk coupling during the spring condition of the task compared to in a stable block condition in people with rLBP compared to back-healthy individuals. When individuals were in active pain, they exhibited more co-activation than when they were in remission, but the co-activation was not greater than in back-healthy individuals.
Circulating Proteome for Pulmonary Nodule Malignancy
Authors: Moez Elham Khodayari , Brhane Yonathan , Warkentin Matthew , Lam Stephen , Field John K , Liu Geoffrey , Montuenga Luis M , Zulueta Javier J , Valencia Karmele , Mesa-Guzman Miguel , Atkar-Khattra Sukhinder , Davies Michael PA , Grant Benjamin , Nialet Andrea Pasquier , Amos Christopher I , Robbins Hilary A , Johansson Mattias , Hung Rayjean J
Published: September 2022

Background

While lung cancer low-dose computed tomography (LDCT) screening is being rolled out in many regions around the world, differentiation of indeterminate pulmonary nodules between malignant and benign remains to a challenge for screening programs. We conducted one of the first systematic investigations of circulating protein markers for their ability to assess the risk of malignancy for screen-detected pulmonary nodules.

Methods

Based on four LDCT screening studies in the United States, Canada and Europe, we assayed 1078 unique protein markers in pre-diagnostic samples based on a nested case-control design with a total of 1253 participants. Protein markers were measured using proximity extension assays and the data were analyzed using multivariate logistic regression, random forest, and penalized regressions.

Results

We identified 36 potentially informative markers differentiating malignant nodules from benign nodules. Pathway analysis revealed a tightly connected network based on the 36 protein-coding genes. We observed a differential mRNA expression profile of the corresponding 36 mRNAs between lung tumors and adjacent normal tissues using data from The Cancer Genomic Atlas. We prioritized a panel of 9 protein markers through 10-fold nested cross-validations. We observed that circulating protein markers can increase sensitivity to 0.80 for nodule malignancy compared to the Brock model (p-value<0.001). Two additional markers were identified that were specific for lung tumors diagnosed within one year. All 11 protein markers showed general consistency in improving prediction across the four LDCT studies.

Conclusions

Circulating protein markers can help to differentiate between malignant and benign pulmonary nodules. Validating these results in an independent CT-screening study will be required prior to clinical implementation.
Thermal spread with Voyant 5 mm Fusion versus LigaSure 5 mm Blunt Tip Devices
Authors: Carmack Austin , Satchell Emma K. , Patel Apar S. , Bashiri Amir , Cagir Burt , Rizzo Anne
Published: September 2022

The authors have withdrawn their manuscript while they perform additional experiments to confirm their findings. Therefore, the authors do not wish for this work to be cited. If you have any questions, please contact the corresponding author.
Exploring the role of the outer subventricular zone during cortical folding through a physics-based model
Authors: Zarzor Mohammad Saeed , Blümcke Ingmar , Budday Silvia
Published: September 2022

The human brain has a highly complex structure both on the microscopic and macroscopic scales. Increasing evidence has emphasized the role of mechanical forces for cortical folding – a classical hallmark of the human brain. However, the link between cellular processes at the microscale and mechanical forces at the macroscale remains insufficiently understood. Recent findings suggest that an additional proliferating zone, the outer subventricular zone (OSVZ), is decisive for the particular size and complexity of the human cortex. To better understand how the OSVZ affects cortical folding, we establish a multifield computational model that couples cell proliferation and migration at the cell scale with growth and cortical folding at the organ scale by combining an advection-diffusion model with the theory of finite growth. We validate our model based on data from histologically stained sections of the human fetal brain. Finally, we address open questions regarding the role of the OSVZ for the formation of cortical folds. The presented framework not only improves our understanding of human brain development, but could eventually help diagnose and treat neuronal disorders arising from disruptions in cellular development and associated malformations of cortical development.
Epidemiology and risk factors for diarrhoeagenic Escherichia coli carriage among children in northern Ibadan, Nigeria
Authors: Akinlabi Olabisi C. , Nwoko El-shama Q. , Dada Rotimi A. , Ekpo Stella , Omotuyi Adeola , Adepoju Akinlolu , Popoola Oluwafemi , Dougan Gordon , Thomson Nicholas R. , Okeke Iruka N.
Published: September 2022

Diarrhea is a leading cause of childhood morbidity in Africa. Outside of multi-country sentinels, of which there are none in Nigeria, few studies focus on bacterial etiology. We performed a case-control study among children under five years of age. Stool specimens were collected from 120 children with, and 357 without, diarrhea attending primary health clinics on the northern outskirts of Ibadan between November 2015 and August 2019. Up to ten E. coli isolates were obtained per specimen and at least three were whole genome-sequenced using Illumina technology. Genomes were assembled using SPAdes, quality evaluated using QUAST, and Virulencefinder was used to identify virulence genes. The microbiological quality of water from 14 wells within the study area was assessed using total and coliform counts. Diarrhoeagenic Escherichia coli (DEC) were isolated from 79 (65.8%) of cases and 217 (60.8%) control children. All DEC pathotypes except Shiga toxin-producing E. coli, a number of hybrid DEC pathotypes, Salmonella and Yersina spp. were detected but no pathogen showed association with disease (p>0.05). Enterotoxigenic E. coli were more commonly recovered from younger controls but exclusively detected in cases aged over nine months. Temporally-linked, highly similar enteroaggregative E. coli were isolated from children in different households in eight instances. No well water sample drawn in the study qualified as potable. Children in northern Ibadan are commonly colonized with DEC. Access to water and sanitation, and vaccines targeting the most abundant pathogens may be critical for protecting children from the less overt consequences of enteric pathogen carriage.
An Evaluation Protocol of ‘Replicability Model’ project for detection and treatment of leprosy and related disability in Chhattisgarh, India
Authors: Darlong Joydeepa , Govindasamy Karthikeyan , Ilozumba Onaedo , Choudhury Sopna , Shrivastva Anjali , Griffiths Frances , Watson Samuel , Sartori Jo , Lilford Richard
Published: September 2022

Introduction

People affected by leprosy are at increased risk of impairments and deformities from peripheral nerve damage. This mostly occurs if diagnosis and treatment is delayed and contributes to continued transmission within the community. Champa district of Chhattisgarh state in India is an endemic area with the highest national annual case detection and disability rates for leprosy. The Replicability Model is a system strengthening intervention implemented by the Leprosy Mission Trust India in Champa that aims to promote early diagnosis and treatment of leprosy, improve on-going management of the effects of leprosy and improve welfare for the people affected by leprosy. This protocol presents a plan to describe the overall implementation of the Replicability Model and describe the barriers and facilitators encountered in the process. We will also quantify the effect of the program on one of its key aims- early leprosy diagnosis.

Methods

We have two Work Packages (WPs). In WP1, we will conduct a process evaluation. This will include three methods i) observations of replicability model implementation teams’ monthly meetings ii) key informant interviews (n=10) and interviews with stakeholders (n=30) iii) observations of key actors (n=15).Our purpose is to describe the implementation process and identify barriers and facilitators to successful implementation.

WP2 will be a quantitative study to track existing and new cases of leprosy using routinely collected data. If the intervention is successful, we expect to see an increase in cases (with a higher proportion detected at an early clinical stage) followed by a decrease in total cases.

Conclusion

This study will enable us to improve and disseminate the Replicability Model by identifying factors that promote success. It will also identify its effectiveness in fulfilling one of its aims: reducing the incidence of leprosy by finding and tracking cases at an earlier stage in the disease.
Meta-Analysis Reveals the Vaginal Microbiome is a Better Predictor of Earlier Than Later Preterm Birth
Authors: Huang Caizhi , Gin Craig , Fettweis Jennifer , Foxman Betsy , Gelaye Bizu , MacIntyre David A. , Subramaniam Akila , Fraser William , Tabatabaei Negar , Callahan Benjamin
Published: September 2022

High-throughput sequencing measurements of the vaginal microbiome have yielded intriguing potential relationships between the vaginal microbiome and preterm birth (PTB; live birth prior to 37 weeks of gestation). However, results across studies have been inconsistent. Here we perform an integrated analysis of previously published datasets from 12 cohorts of pregnant women whose vaginal microbiomes were measured by 16S rRNA gene sequencing. Of 1926 women included in our analysis, 568 went on to deliver prematurely. Substantial variation between these datasets existed in their definition of preterm birth, characteristics of the study populations, and sequencing methodology. Nevertheless, a small group of taxa comprised a vast majority of the measured microbiome in all cohorts. We trained machine learning (ML) models to predict PTB from the composition of the vaginal microbiome, finding low to modest predictive accuracy (0.28-0.79). Predictive accuracy was typically lower when ML models trained in one dataset predicted PTB in another dataset. Earlier preterm birth (<32 weeks, <34 weeks) was more predictable from the vaginal microbiome than late preterm birth (34 - 37 weeks), both within and across datasets. Integrated differential abundance analysis revealed a highly significant negative association betweenL. crispatusand PTB that was consistent across almost all studies. The presence of the majority (18 out of 25) of genera was associated with a higher risk of PTB, withL. iners, Prevotella, andGardnerellashowing particularly consistent and significant associations. Some example discrepancies between studies could be attributed to specific methodological differences, but not most study-to-study variations in the relationship between the vaginal microbiome and preterm birth. We believe future studies of the vaginal microbiome and PTB will benefit from a focus on earlier preterm births, and improved reporting of specific patient metadata shown to influence the vaginal microbiome and/or birth outcomes.
A 1D Model Characterizing the Role of Spatiotemporal Contraction Distributions on Lymph Transport
Authors: Sedaghati Farbod , Dixon J. Brandon , Gleason Rudolph L.
Published: September 2022

Background

Lymphedema is a condition in which the two primary functions of the lymphatic system, immunity and lymph transport, are compromised. Computational models of lymphatic function to characterize lymph transport have proved useful in quantifying changes in lymph transport in health and disease; however, much is unknown regarding the regulation of contractions throughout a lymphatic network. The purpose of this paper is to study the role of pacemaking cells and contractile wave propagation on lymph transport using a 1-D mathematical model.

Method

A 1D fluid-solid modeling framework with constitutive relationships were employed to characterize the interaction between the contracting vessel wall and the lymph flow during contractions. The time-space distribution of contraction waves along the length of a three-lymphangion chain, was determined by prescribing the location of pacemaking cells and parameters that govern the contractile wave propagation, with the total contractile response at each location determined as the summation of the local electrical signals.

Results

Spatiotemporal changes in radius and lymphangion ejection fraction from our illustrative simulations mimic well values reported in isolated lymphatics from the wild-type (WT) and Smmhc-CreERT2;Cx45fx/fx knock-out (KO) reported in the literature. The flow rate is 5.43 and 2.45 μL/hr in the WT and the KO (average) models, respectively. The average and the peak WSS in the WT model are 0.08 and 4 dyn/cm2 and −0.03 and 0.87 dyn/cm2 in the KO (average) models, respectively.

Conclusions

The factors that govern the timing of lymphatic contractions remain largely unknown; but these factors likely play a central role in health and disease. This modeling framework captures well lymphatic contractile wave propagations and how it relates to lymph transport and may motivate novel assays and experimental endpoints to evaluate subtle changes in lymphatic pumping function in the development and progression of lymphedema.
DNA methylation at a single cytosine embedded in the W-box cis-element repels binding of WRKY transcription factors through steric hindrance
Authors: Charvin Magali , Halter Thierry , Blanc-Mathieu Romain , Barraud Pierre , Aumont-Nicaise Magali , Parcy François , Navarro Lionel
Published: September 2022

Previously, we showed that the Arabidopsis active demethylase ROS1 prunes DNA methylation at the promoters of a subset of immune-responsive genes to facilitate their transcriptional activation during antibacterial defence (Halter et al., 2021). In particular, ROS1 was shown to demethylate the RLP43 promoter in a region carrying a functional W-box cis-element, thereby ensuring a tight binding of WRKY transcriptional factors (TFs) onto DNA. Here, we first extend these findings by showing that DNA methylation at W-box elements decreases the binding of several Arabidopsis WRKY TFs in vitro. Furthermore, we provide evidence that DNA methylation at a single cytosine located in the W-box of the RLP43 promoter strongly repels DNA binding of an Arabidopsis WRKY TF in vitro. Using structural modelling, we demonstrate that this cytosine interacts through van der Waals contacts with the conserved tyrosine of WRKY DNA binding domains. Significantly, our model predicts steric hindrance when a 5-methyl group is present on this specific cytosine, thereby likely preventing tight binding of WRKY DNA binding domains. Finally, because the WRKY motif and the residues involved in DNA contacts are conserved, we propose that this methylation-dependent WRKY-DNA binding inhibitory mechanism must be widespread across plant species.
The maternal brain is more flexible and responsive at rest: effective connectivity of the parental caregiving network in postpartum mothers
Authors: Orchard Edwina R , Voigt Katharina , Chopra Sidhant , Thapa Tribikram , Ward Phillip GD , Egan Gary F , Jamadar Sharna D
Published: September 2022

The field of neuroscience has largely overlooked the impact of motherhood on brain function outside the context of responses to infant stimuli. Here, we apply spectral dynamic causal modelling (spDCM) to resting-state fMRI data to investigate differences in brain function between a group of 40 first-time mothers at one-year postpartum and 39 age- and education-matched women who have never been pregnant. Using spDCM, we investigate the directionality (top-down vs bottom-up) and valence (inhibition vs excitation) of functional connections between six key brain regions implicated in motherhood: the dorsomedial prefrontal cortex, ventromedial prefrontal cortex, posterior cingulate cortex, parahippocampal gyrus, amygdala, and nucleus accumbens. We show a selective modulation of inhibitory pathways related to differences between (1) mothers and non-mothers, (2) the interactions between group and cognitive performance and (3) group and social cognition, and (4) differences related to maternal caregiving behaviour. Across analyses, we show consistent disinhibition between cognitive and affective regions suggesting more efficient, flexible, and responsive behaviour, subserving cognitive performance, social cognition, and maternal caregiving. Together our results support the interpretation of these key regions as constituting a parental caregiving network. The nucleus accumbens and the parahippocampal gyrus emerging as ‘hub’ regions of this network, highlighting the global importance of the affective limbic network for maternal caregiving, social cognition, and cognitive performance in the postpartum period.
GOLVEN peptides regulate lateral root spacing as part of a negative feedback loop on the establishment of auxin maxima
Authors: Jourquin Joris , Fernandez Ana Ibis , Xu Ke , Šimura Jan , Ljung Karin , Beeckman Tom
Published: September 2022

The initiation of lateral roots in Arabidopsis requires the accumulation of auxin in lateral root founder cells, yielding a local auxin maximum. The positioning of these auxin maxima along the primary root determines the density and spacing of lateral roots. The GOLVEN6 (GLV6) and GLV10 signaling peptides and their receptors have been established as regulators of lateral root spacing via an inhibitory effect on lateral root initiation. However, it remained unclear how these GLV peptides interfere with auxin signaling or homeostasis. Here we show that GLV6/10 signaling regulates the expression of a subset of auxin response genes during lateral root initiation, downstream of the canonical auxin signaling pathway, while simultaneously inhibiting the establishment of auxin maxima in xylem-pole pericycle cells. We present genetic evidence that this inhibitory effect relies on the activity of the PIN3 and PIN7 auxin export proteins. Furthermore, GLV6/10 peptide signaling was found to enhance PIN7 abundance in the plasma membrane of xylem-pole pericycle cells, which likely stimulates auxin efflux from these cells. Based on these findings, we propose a model in which the GLV6/10 signaling pathway serves as a negative feedback loop that contributes to the robust patterning of auxin maxima along the primary root.
Impact of vancomycin loading doses and dose escalation on glomerular function and kidney injury biomarkers in a translational rat model
Authors: Chang Jack , Pais Gwendolyn M. , Engel Patti L. , Klimek Patryk , Marianski Sylwia , Valdez Kimberly , Scheetz Marc H.
Published: September 2022

Vancomycin induced kidney injury is common, and outcomes in humans are well predicted by animal models. This study employed our translational rat model to investigate temporal changes in glomerular filtration rate (GFR) and correlation with kidney injury biomarkers related to various vancomycin dosing strategies. First, Sprague Dawley rats received allometrically scaled loading doses or standard doses. Rats that received a loading dose had lower GFR and increased urinary injury biomarkers (kidney injury molecule 1 [KIM-1] and clusterin) that persisted through day 2, compared to those that did not receive a loading dose. Second, we compared low and high allometrically scaled vancomycin doses to a positive acute kidney injury control of high dose folic acid. Rats in both the low and high vancomycin dose groups had higher GFRs on all dosing days versus the positive control group. When the two vancomycin groups were compared, rats that received the low dose had significantly higher GFR on days 1, 2, and 4. Compared to low dose vancomycin, KIM-1 was elevated in high dose rats on dosing day 3. GFR correlated most closely with the urinary injury biomarker KIM-1, on all experimental days.

Vancomycin loading doses were associated with significant loss of kidney function and elevation of urinary injury biomarkers. In our translational rat model, both the degree of kidney function decline and urinary biomarker rise corresponded to the magnitude of vancomycin dose (i.e. higher dose resulted in more kidney function decline and greater degree of urinary injury biomarker increase).
Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study
Authors: Leavy Olivia C , Kawano-Dourado Leticia , Stewart Iain D , Quint Jennifer K , Solomon Joshua J , Borie Raphael , Crestani Bruno , Wain Louise V , Jenkins R Gisli , Dieudé Philippe , Minelli Cosetta
Published: September 2022

Introduction

A usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA) related Interstitial Lung Disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors.

Methods

We used two-sample bidirectional Mendelian Randomisation (MR) to investigate the causal effects of RA on UIP and of UIP on RA, using variants from genome-wide association studies of RA (separately for seropositive and seronegative RA) and of IPF as genetic instruments. We conducted inverse-variance-weighted fixed-effect MR as a primary analysis and undertook sensitivity analyses to assess potential violations of the key MR assumption of no (horizontal) pleiotropy.

Results

Seropositive RA showed a significant protective effect on IPF (Odds Ratio, OR = 0.93; 95% Confidence Interval, CI: 0.87-0.99; P=0.032), while the MR in the other direction showed a strongly significant causal effect of IPF on seropositive RA (OR = 1.06, 95% CI: 1.04-1.08, P=1.22×10−11).

Conclusion

Our findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between IPF and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The causal effect of IPF on seropositive RA suggests that patho-mechanisms involved in the development of UIP may promote RA and would suggest that screening for UIP in asymptomatic RA patients may be warranted and may influence therapy management of patients with RA-UIP.
Major Contribution of Myeloid Cells In TB specific Host Gene Signature: Revelations from Re-Analysis of Publicly Available Datasets
Authors: Gautam Anuradha , Mohapatra Saroj Kant , Pandit Bhaswati
Published: September 2022

Introduction

Interaction of human host and its pathogen M.tuberculosis drives tuberculosis disease, resulting in dysregulation of host gene expression. We re-analyzed host gene expression datasets of TB to identify and validate a cellular circuit by interlinking the DEGs with their target miRNAs, GWAS hits associated with immunological phenotypes mapping to the DEGs and associated cellular subtypes through bioinformatic and experimental approaches.

Methodology

DEGs were identified systematically through re-analysis of whole blood host transcriptomic datasets of treatment-naive TB patients, obtained from public repositories having at least 1.2 fold change of expression and FDR corrected p-value <0.05. Using well characterized M.tb antigens: Ag85 complex, LAM, CFP10 and ESAT6, we evaluated their effect on the expression of a subset of the top DEGs with at least two fold change of expression in a monocytic cell line THP1 with or without differentiation into a macrophage-like state with PMA and a T cell line Jurkat E6-1.

Results

We discovered 305 DEGs (236 up and 69 down-regulated genes) out of which 23 (21 up and 2 down-regulated genes) were top DEGs. Overall, innate immune and myeloid cell associated pathways were enriched for up-regulated genes while T cell associated pathways were enriched for down-regulated genes. Among top DEGs, EPSTI1 was predominantly up-regulated in macrophages while SERPING1 was universally up-regulated in the monocyte model by all antigens. The down-regulation of gene expression was replicated by ESAT6 in T cell line by significantly down-regulating a top down-regulated gene LRRN3.