bluuebunny/crossref_metadata_2025 huggingface dataset:
Models of Care for Postacute COVID-19 Clinics
Authors: Verduzco-Gutierrez Monica , Estores Irene M. , Graf Min Jeong P. , Barshikar Surendra , Cabrera Juan A. , Chang Lynn E. , Eapen Blessen C. , Bell Kathleen R.
Published: October 2021

After surviving infection with the SARS-CoV-2 virus, individuals may have persistent symptoms and prolonged impairments that may last for weeks to months. The frequency and heterogeneity of persistent post-COVID conditions have created challenges in care. Specialty clinics are being established in response to an increasing need to care for patients with postacute sequelae of SARS-CoV-2 or long COVID syndrome. Although many post-COVID conditions can be bettered through a comprehensive rehabilitation plan, various clinical settings may benefit from differing models of coordinated care. We present five models of care in varying degrees of development and compare processes and adaptations to address the unique needs of each center and their unique patient populations. Forging a path to recovery will necessitate a multidisciplinary team with physiatry involvement to meet the distinctive needs of patients with postacute sequelae of SARS-CoV-2. Furthermore, it is imperative that there be equitable access to this care and commitment from healthcare institutions to provide resources for these programs.
Hamstring Muscle Cramp Visualized on Bone Single-Photon Emission Computed Tomography/Computed Tomography Hybrid Imaging
Authors: Tsiouris Spyridon , Xourgia Xanthi , Tsironi Maria , Sakellariou Constantinos , Fotopoulos Andreas
Published: October 2021

It is well recognized that bone-seeking radiotracers localize in muscles sustaining an injury from various causes (e.g., strenuous physical activity, trauma, hereditary myopathies, inflammatory myositides, medications, electrical burns, etc.). This report presents the case of an active 50-yr-old man (body mass index = 29) that was recently referred to our nuclear medicine department for bone scintigraphy, for the skeletal staging of a newly diagnosed prostate adenocarcinoma. The scan findings were unremarkable for its oncological indication but revealed extraosseous radiotracer absorption in the medial region of the hamstrings bilaterally. Hybrid scintitomography (single-photon emission computed tomography) with computed tomography indicated that this uptake involved the semitendinosus muscle. On a more meticulous repeat history questioning, he recalled experiencing muscle cramps on both posterior thighs 5 days earlier, during intense work-related physical activity (plumbing) under warm environmental conditions. The combination of strenuous exercise with likely dehydration contributed to bilateral self-limiting heat cramps of the hamstrings, leading to an inconsequential localized minor rhabdomyolysis that was discovered coincidentally a few days later during a bone scan. Although extraskeletal absorption of bone-seeking radiotracers in muscles is widely documented as a result of exertion or injury, this is the first report of radiotracer absorption induced by cramping.
Patient Preferences for Rituximab Additional Risk Minimization Measures: Results From an International Online Survey
Authors: Schneiderova Kristyna , Bere Nathalie , Stenver Doris Irene , Straus Sabine M. J. M.
Published: October 2021

Objective

Patients’ opinions are essential in optimizing risk minimization measures (RMMs) because they bring their real-life experience of disease management and medicines’ use into the regulatory assessments. The aim of the survey launched in 2018 by the European Medicines Agency, in collaboration with the Pharmacovigilance Risk Assessment Committee, was to consult targeted patient groups treated with rituximab for nononcology indications to evaluate their preferences on how to receive information on progressive multifocal leukoencephalopathy and (serious) infections. Additional RMMs such as educational materials for physicians and patients including a patient alert card (PAC) and a patient brochure (PB) are in place to minimize these risks.

Methods

A question-based online survey in English created on the EU-Survey platform and disseminated primarily via relevant European patient organizations.

Results

Most patients (47 of 61) had knowledge of these potential adverse effects. Mostly, they were informed by a healthcare professional. Both a PAC and a PB were supported as useful tools to raise awareness of these adverse effects and thus minimize the potential risks among patients. Where the participants had to choose only 1 of these educational materials, 43 of them preferred a PAC, a shorted description that is always held by the patient and reaches the relevant healthcare professional when needed.

Conclusions

Collecting patients’ preferences supports periodic assessment of additional RMMs and increase transparency of regulatory processes. Considering the limitations of this initial survey, further investigation is needed to generalize the results into patients’ safety outcomes.
Safety of High-Intensity, Low-Volume Interval Training or Continuous Aerobic Training in Adults With Metabolic Syndrome
Authors: Gallo-Villegas Jaime , Restrepo Daniel , Pérez Laura , Castro-Valencia Leonardo A. , Narvaez-Sanchez Raúl , Osorio Jorge , Aguirre-Acevedo Daniel C. , Calderón Juan C.
Published: October 2021

Objective

The aim of the study was to evaluate the safety of high-intensity, low-volume interval training (HIIT-low volume) compared with moderate-intensity continuous aerobic training (MICT) in adults with metabolic syndrome.

Methods

This is a controlled, randomized, clinical trial in patients without history of ischemic heart disease or diabetes, who underwent a supervised, 3 sessions/week, 12-week treadmill exercise program. The HIIT-low volume (n = 29) sessions consisted of 6 intervals with 1-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). The MICT (n = 31) trained at 60% of VO2peak for 30 minutes. A new approach to record and classify all clinical events according to possible causality based on Naranjo’s algorithm was developed.

Results

Patients were 50.8 ± 6.0 years old, 70% women, with body mass index of 30.6 ± 4.0 kg/m2 and VO2peak of 29.0 ± 6.3 mL·kg−1·min−1. In total, 60 clinical events were recorded in the HIIT-low volume group and 48 in the MICT group, with 59.3% classified as general disease. Only 21 events were classified as adverse reactions possibly related to exercise, without any serious adverse reactions. Both interventions had a similar incidence of musculoskeletal events (incidence rate ratio, 1.1; 95% confidence interval, 0.6–1.8), but HIIT-low volume had a higher incidence of cardiovascular events (incidence rate ratio, 2.9; 95% CI, 0.4–22.8) after adjusting for age, sex, and body mass index (HIIT-low volume: chest pain [n = 1] and symptoms of venous insufficiency of lower limbs [n = 2]; MICT: chest pain [n = 1]).

Conclusions

The HIIT-low volume and MICT are safe in patients with metabolic syndrome. We recommend a muscle-conditioning program prior to both and to avoid HIIT-low volume in treadmill in patients with venous insufficiency of the lower limbs.

Trial registration number NCT03087721.
Endoscopic Endonasal Reconstruction Using a Pedicled Middle Turbinate Flap for Spontaneous Cerebrospinal Fluid Rhinorrhea
Authors: Takahara Kento , Ueda Ryo , Toda Masahiro
Published: October 2021

Although endoscopic skull-base reconstruction protocols to reduce cerebrospinal fluid (CSF) leakage are reported, the most effective management strategies have not been determined. We describe the successful repair of a spontaneous CSF leak using a vascularized middle turbinate flap (MTF) via an endonasal endoscopic approach and also discuss the effective reconstruction with other available pedicled flaps. An 11-year-old girl had a 5-month history of intermittent CSF rhinorrhea. Endoscopic endonasal skull base reconstruction was performed using the pedicled MTF technique, which sufficiently covered the unilateral cribriform plate and ethmoidal fovea including suspicious leakage site. Middle turbinate flaps may be good for repairing spontaneous CSF leaks, which commonly have small, low-flow CSF fistulas around a cribriform plate. As spontaneous CSF leaks are known to have a higher recurrence rate, MTF may be advantageous because more of the normal structures are retained.
Airway Compromise in Mandibular Fracture
Authors: Sasaki Ryo , Togashi Chika , Miyamoto Noriko Sangu , Okamoto Toshihiro
Published: October 2021

Airway compromise is life threatening complication in the maxillofacial fracture. However, the incident of the airway compromise following mandibular fracture was little known. Maxillofacial fractures during the past 3 years from 2017 to 2020 were investigated retrospectively. There were 154 patients with maxillofacial fractures were noted in the past 3 years. Mandibular fractures accounted for 93% of the maxillofacial fracture. The most common cause of injury was falls (75%), followed by sports (12%). Of these, 3 cases (1.9%) needed an airway management at the time of initial treatment, and all were mandibular fractures. The average age was 55.7 ± 10 years and all were male. The cause of the injury was high-energy trauma including traffic accident and work-related injury. Endotracheal intubation was performed at the time of initial treatment. All cases were communicated mandibular fracture included symphysis and para-symphysis region, and the bone fragments including the genial tubercle were largely displaced inward.
Long Term Speech and Feeding Outcomes in Patients With Pierre Robin Sequence
Authors: Morzycki Alexander , Budden Curtis , Skulsky Samuel , Cuglietta Loredana , Guilfoyle Regan
Published: October 2021

Objective:

Airway obstruction in newborns with Pierre Robin sequence (PRS) may be managed with tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), or tracheostomy to prevent airway compromise when conservative airway interventions fail or are contraindicated based on the type of obstruction present. Unfortunately, some of these procedures have the potential to affect a child's speech and feeding development.

Method:

The authors retrospectively reviewed the records of all children with PRS treated at our institution in the last 25 years. Our primary outcomes of interests were: (1) consonant production errors; (2) achievement of full oral feeds; (3) need for prolonged gastrostomy tube feeds; and (4) avoidance of tracheostomy.

Results:

Seven (7/73, 10%) children required intubation at birth for respiratory failure. Forty-two children were treated with TLA (42/73, 58%), 2 with MDO (2/73, 3%), and 1 (1/73, 1%) with tracheostomy. Twenty-one (21/73, 29%) were treated with conservative airway interventions. Of the 7 children requiring intubation, 1 required tracheostomy, and 6 required TLA. Five children who received TLA initially proceeded to tracheostomy. Of the 3 children who underwent MDO, 2 required tracheostomy. Of the 2 patients who underwent MDO, 2 failed, requiring tracheostomy. One child required tracheostomy as the first airway intervention. Among all children with PRS, /s,z/ speech errors were the most common. Children treated with conservative airway interventions had significantly fewer /sh/ errors at age 3 (X = 6.604, P < 0.05) relative to those treated with TLA, MDO, and/or tracheostomy. Consonant production errors extinguished over time, with significantly less /s,z/ errors produced at age 8 compared to at ages 3 (Z = −2.263, P < 0.01), 4 (Z = −2.449, P < 0.05), 5 (Z = −2.775, P < 0.01), and 6 (Z = −2.049, P < 0.05). Among all children, 70% (51/70) were able to achieve full oral feeds.

Conclusions:

This study describes speech-production and feeding outcomes in children with PRS. Tongue-tip sound errors, including /s,z/, are prominent early in speech development but later extinguish, a pattern of speech maturation that follows that of typically-developing children.

Most children were able to achieve full oral feeds, with few requiring prolonged g-tube placement. We hope these results serve as a useful tool in managing speech and feeding in children with TLA, and when counselling patients with PRS requiring definitive airway surgery.
Intravenous Tranexamic Acid is Associated With a Clinically Significant Reduction in Blood Loss in Craniosynostosis Surgery
Authors: Varidel Alistair , Cooper Michael , Loughran Janet , Menezes Minal , Marucci Damian
Published: October 2021

Blood loss is a potential cause of morbidity and mortality in craniosynostosis surgery. Recent reports have suggested that the use of tranexamic acid (TXA), an antifibrinolytic agent, mitigates this blood loss. A retrospective cohort study of patients undergoing craniosynostosis surgery at a tertiary craniofacial hospital in Sydney was undertaken. Primary outcomes were blood loss and transfusion requirements. Two groups were compared: those who received intravenous prophylactic TXA and those who underwent surgery without TXA. Statistical analysis was performed with Student t test and the Mann–Whitney U test for nonparametric results. We identified 206 patients who underwent craniosynostosis surgery over an 8 year period; 78 control patients and 128 patients that received TXA. Tranexamic acid was found to result in a weight-adjusted calculated blood loss mean difference of 9.6 ml/kg across all procedures (P = 0.0332 95% confidence interval 0.7734–18.4266). The actual blood loss reduction achieved with TXA was 6.7 ml/kg in spring cranioplasties, compared to 15.2 ml/kg in fronto-orbital remodeling procedures. There was a statistically and clinically significant reduction in postoperative transfusion incidence, with transfusions required in 27% of controls and 6% of TXA patients (P < 0.0001). The number needed to treat to prevent giving a unit of blood postoperatively was 4.8. There were no incidences of TXA-specific complications. This study found that TXA is a safe and effective method of decreasing blood loss and transfusion requirements in patients undergoing craniosynostosis surgery. The clinical benefit of TXA is particularly evident in the more invasive craniosynostosis surgeries.
Massive Brain Swelling Following Reduction Cranioplasty for Secondary Turricephaly
Authors: Yaacobi Dafna Shilo , Kershenovich Amir , Ad-El Dean , Shachar Tal , Shay Tamir , Olshinka Asaf
Published: October 2021

Cranioplasty is commonly performed to treat craniosynostosis. A rare postsurgical complication is massive brain swelling with elevated intracranial pressure. This commonly presents with mydriasis, coma, and seizures; radiologic findings include cerebral edema, parenchymal hemorrhages, and ischemic changes.

The authors describe a 9-year-old boy who developed massive brain swelling following reduction cranioplasty for secondary turricephaly. His history included surgical repair of metopic-craniosynostosis at age 5.5 months, by means of an anterior cranial-vault reconstruction with fronto-orbital advancement. After presenting to our clinic with a significant turricephalic skull deformity, he underwent cranial reduction cranioplasty. On postoperative day 1, mild neurological signs associated to increased intracranial pressure were noticed. As they worsened and massive brain swelling was identified, he was treated pharmacologically. On postoperative day 13, the patient was operated for decompression.

A literature review yielded 4 articles related to massive brain swelling for post-traumatic craniectomies. None described elevated intracranial pressure or massive brain swelling following cranial reduction for secondary craniosynostosis. The main dilemma regarding our patient was the necessity and timing of a second operation.

The literature did not reveal relevant recommendations regarding treatment timing nor preventative measures.

The authors recommend presurgical neuro-ophthalmological and imaging evaluation, for comparisons and management during the immediate and short-term follow-ups. The authors suggest that for a patient presenting with signs and symptoms of cerebral edema or high intracranial pressure following reduction-cranioplasty, pharmacological treatment should be initiated promptly, and careful drainage and eventual surgical-treatment should be considered if no improvement is shown in the subsequent days.
Variations in Paranasal Sinus Anatomy in Children With Apert Syndrome: A Radiological Analysis
Authors: Turgut Nesrettin Fatih , Hogg Emma S. , De Sujata , Sharma Sunil D. , Avula Shivaram
Published: October 2021

Background:

Apert syndrome is a genetic disorder characterized by craniofacial abnormalities and premature closure of the coronal sutures. The restriction of cranial development may have a subsequent effect on paranasal anatomy development.

Aim:

The aim of the study was to gain an understanding of paranasal sinus anatomical variations seen in children with Apert syndrome.

Materials and Methods:

This was a retrospective review of computed tomography and magnetic resonance images of children with Apert syndrome from 2000 to 2020. Images were reviewed to identify anatomical variations in paranasal sinus anatomy.

Results:

Twenty-one patients were included in the study. The most commonly seen variation was septal deviation in 86% of cases, with 60% of patients having a septal defect. The presence of protrusion or dehiscence of the infraorbital nerve, carotid canal and Vidian nerve, and presence of a concha bullosa were not observed in any patients. Keros type I was the most commonly observed olfactory fossa depth in 79% of patients, and type I Kuhn cells were observed in 83% of patients.

Conclusions:

To our knowledge, this is the first study which describes the prevalence of variations in paranasal sinus anatomy found in children with Apert syndrome. Septal deviation, type I Kuhn cells and Keros type I olfactory fossa depth were observed in a higher prevalence in our cohort than in the general population. As such, assessment for the presence of chronic rhinosinusitis and nasal obstruction should be evaluated as part of the multidisciplinary assessment.
Resurfacing of Face and Neck Using Superthin Thoracodorsal Artery Perforator Free Flaps
Authors: Chang Lan Sook , Lim Jung Han , Kim Youn Hwan
Published: October 2021

Background:

Resurfacing of facial and neck defects is challenging due to the unique skin color, texture, and thickness of the region. With the development of microsurgical reconstruction, perforator- free flaps can provide adequate soft tissue. However, despite various modifications, such flaps hardly satisfy cosmetic requirements, due to differences in color and bulkiness. We have used superthin thoracodorsal artery perforator (TDAp) free flaps to overcome these limitations.

Methods:

Between January 2012 and January 2020, 15 patients underwent reconstructive procedures for facial and neck soft tissue defects using superthin TDAp free flaps. First a perforator was found above the deep fascia and a flap was elevated over the superficial fascia layer. A process named “pushing with pressure and cutting” was carried out before pedicle ligation until all the superficial fat tissue had been removed except for around the perforator. Patient satisfaction was evaluated using a questionnaire about color, contour, and overall satisfaction a minimum of 12 months after surgery.

Results:

Flap size ranged from 6 × 4 cm to 25 × 14 cm (mean, 126.3 cm2). Final flap thickness ranged from 4 to 6 mm. (mean, 4.97 mm). All flaps survived without any loss and there were no flap-related complications. After a mean follow-up period of 14.4 months, patients were satisfied with the aesthetic results, and cervical range of motion increased by 11.25 degree on average in burn scar contracture patients.

Conclusions:

The superthin TDAp free flap is an excellent alternative to face and neck resurfacing, providing a large and thin flap with excellent color matching and good vascularity.
Needlescopic Disconnection and Peritoneal Closure for Pediatric Inguinal Hernia Repair: A Novel Technique
Authors: Shalaby Rafik , Negm Mohamed , El-Sawaf Mohamed , Elsaied Adham , Shehata Sherif , Hamed Ashraf , Shehata Sameh , Radwan Ahmed B.
Published: October 2021

Background:

There are many laparoscopic techniques for pediatric congenital inguinal hernia repair. Needlescopic surgery was introduced recently in pediatric patients aiming at getting excellent cosmetic outcomes.

Purpose:

The aim of this study was to describe a novel technique for needlescopic inguinal hernia repair in children.

Patients and Methods:

Needlescopic division of the hernial sac was carried out on 369 children in 6 pediatric tertiary centers during the period from August 2016 to May 2019. All hernias were repaired by a novel needlescopic procedure that replicates all the steps of the open herniotomy.

Results:

A total of 369 patients with 410 hernias were included in this study. They were 232 (62.9%) males and 137 (37.1%) females, with a mean age of 3.58±1.26 (range=2 to 8 y) and mean internal inguinal ring diameter was 13.65±3.85 mm (range=8 to 20 mm). The mean operative time was 23.36±4.67 minutes for bilateral and 14.28±2.98 minutes for unilateral cases. All cases were completed without conversion to conventional laparoscopy. All cases were followed up for a mean of 19.6±3.2 months. None of our patients developed recurrence or testicular atrophy and the scars were nearly invisible 3 months postoperatively.

Conclusions:

Needlescopic pediatric inguinal hernia repair using disconnection of the hernia sac at internal inguinal ring with purse-string suture closure of peritoneum is feasible and safe with no recurrence and with outstanding cosmetic results.
Development of a Simplified Patient-Centered Pelvic Floor Surgery Complication Scale
Authors: Fitzgerald Jocelyn , Richter Holly E. , Sung Vivian , Dunivan Gena , Mete Mihriye , Gutman Robert E.
Published: October 2021

Objectives

There does not currently exist a complication scale to evaluate pelvic reconstructive surgery (PRS) that takes in account patient-centered outcomes. The purpose of this study was to characterize and compare patient and surgeon responses to a simplified, patient-centered version of the previously described Pelvic Floor Complication Scale (PFCS).

Methods

This is a multicenter (4 female pelvic medicine and reconstructive surgery practices) cross-sectional study of patients and surgeons. Using focus groups and telephone surveys, the original PFCS questionnaire was simplified. One hundred and twenty-four patients were recruited 6–12 months after PRS. Fifty-seven surgeons were recruited via electronic questionnaires. Surgeons and patients were asked to rank the severity and bother of each complication on a scale of 0 to 5 (0, none; 1, mild; 3, moderate; 5, major).

Results

Patients rated bother higher than severity for 36 of 38 complications (all differences ≤0.5 points). For statistical analysis, the highest response to patient bother/severity was chosen to weigh in favor of the patient. Patient bother/severity scores were significantly different (±0.5 points) for 27 of 38 complications compared with surgeon responses. Surgeon scores were higher for 5 complications (0.5–1.9 point differences) related to major injury requiring repair and wound breakdown. Patient scores were higher for 22 complications with the highest differences related to dyspareunia, constipation, or new/persistent urinary incontinence.

Conclusions

This mixed methods investigation revealed key differences between how patients and surgeons value PRS complications. Surgeons scored major surgical injuries higher than patients, whereas patients rated issues that many surgeons consider quality-of-life outcomes higher due to potential long-term bother. These data will be used to create a simplified, patient-centered PFCS.
Regulation of EGFR signalling by palmitoylation and its role in tumorigenesis
Authors: Kadry Yasmin A. , Lee Jia-Ying , Witze Eric S.
Published: October 2021

The epidermal growth factor receptor (EGFR) is an essential driver of oncogenic signalling, and EGFR inhibitors are some of the earliest examples of successful targeted therapies in multiple types of cancer. The tractability of EGFR as a therapeutic target is overshadowed by the inevitable drug resistance that develops. Overcoming resistance mechanisms requires a deeper understanding of EGFR regulation in cancer cells. In this review, we discuss our recent discovery that the palmitoyltransferase DHHC20 palmitoylates EGFR on the C-terminal domain and plays a critical role in signal regulation during oncogenesis. Inhibiting DHHC20 expression or mutating the palmitoylation site on EGFR alters the EGF-induced signalling kinetics from a transient signal to a sustained signal. The change in signalling is accompanied by a decrease in cell proliferation in multiple human cancer cell lines. Our
in vivo
studies demonstrate that ablating the gene
Zdhhc20
by CRISPR/Cas9-mediated inhibition in a mouse model of oncogenic Kras-driven lung adenocarcinoma potently inhibits tumorigenesis. The negative effect on tumorigenesis is mediated by EGFR since the expression of a palmitoylation-resistant mutant form of EGFR also inhibits Kras-driven lung adenocarcinoma. Finally, reducing EGFR palmitoylation increases the sensitivity of multiple cancer cell lines to existing inhibitors of EGFR and downstream signalling effector pathways. We will discuss the implications of these effects and strategies for targeting these new vulnerabilities.
BRCA1-BARD1 regulates transcription through modulating topoisomerase IIβ
Authors: Bunch Heeyoun , Jeong Jaehyeon , Kang Keunsoo , Jo Doo Sin , Cong Anh T. Q. , Kim Deukyeong , Kim Donguk , Cho Dong-Hyung , Lee You Mie , Chen Benjamin P. C. , Schellenberg Matthew J. , Calderwood Stuart K.
Published: October 2021

RNA polymerase II (Pol II)-dependent transcription in stimulus-inducible genes requires topoisomerase IIβ (TOP2B)-mediated DNA strand break and the activation of DNA damage response signalling in humans. Here, we report a novel function of the breast cancer 1 (BRCA1)-BRCA1-associated ring domain 1 (BARD1) complex in this process. We found that BRCA1 is phosphorylated at S1524 by the kinases ataxia-telangiectasia mutated and ATR during gene activation, and that this event is important for productive transcription. Our biochemical and genomic analyses showed that the BRCA1-BARD1 complex interacts with TOP2B in the
EGR1
transcription start site and in a large number of protein-coding genes. Intriguingly, the BRCA1-BARD1 complex ubiquitinates TOP2B, which stabilizes TOP2B binding to DNA while BRCA1 phosphorylation at S1524 controls the TOP2B ubiquitination by the complex. Together, these findings suggest the novel function of the BRCA1-BARD1 complex in the regulation of TOP2B and Pol II-mediated gene expression.
Analysing the impact of electrification on rural attractiveness in Senegal with mobile phone data
Authors: Salat Hadrien , Schläpfer Markus , Smoreda Zbigniew , Rubrichi Stefania
Published: October 2021

Reliable and affordable access to electricity has become one of the basic needs for humans and is, as such, at the top of the development agenda. It contributes to socio-economic development by transforming the whole spectrum of people’s lives—food, education, healthcare. It spurs new economic opportunities, thus improving livelihoods. Using a comprehensive dataset of pseudonymized mobile phone records, we analyse the impact of electrification on attractiveness for rural areas in Senegal. We extract communication and mobility flows from call detail records and show that electrification is positively and specifically correlated with centrality measures within the communication network and with the volume of incoming visitors. This increased influence is however circumscribed to a limited spatial extent, creating a complex competition with nearby areas. Nevertheless, we found that the volume of visitors between any two sites could be well predicted from the level of electrification at the destination and the living standard at the origin. In view of these results, we discuss how to obtain the best outcomes from a rural electrification planning strategy. We determine that electrifying clusters of rural sites is a better solution than centralizing electricity supplies to maximize the development of specifically targeted sites.
Ecological ramifications of adaptation to size-selective mortality
Authors: Evangelista Charlotte , Dupeu Julia , Sandkjenn Joakim , Pauli Beatriz Diaz , Herland Anders , Meriguet Jacques , Vøllestad Leif Asbjørn , Edeline Eric
Published: October 2021

Size-selective mortality due to harvesting is a threat to numerous exploited species, but how it affects the ecosystem remains largely unexplored. Here, we used a pond mesocosm experiment to assess how evolutionary responses to opposite size-selective mortality interacted with the environment (fish density and light intensity used as a proxy of resource availability) to modulate fish populations, prey community composition and ecosystem functions. We used medaka (
Oryzias latipes
) previously selected over 10 generations for small size (harvest-like selection; small-breeder line) or large size (large-breeder line), which displayed slow somatic growth and early maturity or fast somatic growth and late maturity, respectively. Large-breeder medaka produced more juveniles, which seemed to grow faster than small-breeder ones but only under high fish density. Additionally, large-breeder medaka had an increased impact on some benthic prey, suggesting expanded diet breadth and/or enhanced foraging abilities. As a consequence, increased light stimulated benthic algae biomass only in presence of large-breeder medaka, which were presumably better at controlling benthic grazers. Aggregated effect sizes at the community and ecosystem levels revealed that the ecological effects of medaka evolution were of similar magnitude to those induced by the environment and fish introduction. These findings indicate the important environmental dependency of evolutionary response to opposite size-selective mortality on higher levels of biological organizations.
Pendraig milnerae, a new small-sized coelophysoid theropod from the Late Triassic of Wales
Authors: Spiekman Stephan N. F. , Ezcurra Martín D. , Butler Richard J. , Fraser Nicholas C. , Maidment Susannah C. R.
Published: October 2021

We describe a new small-bodied coelophysoid theropod dinosaur,Pendraig milneraegen. et sp. nov, from the Late Triassic fissure fill deposits of Pant-y-ffynnon in southern Wales. The species is represented by the holotype, consisting of an articulated pelvic girdle, sacrum and posterior dorsal vertebrae, and an associated left femur, and by two referred specimens, comprising an isolated dorsal vertebra and a partial left ischium. Our phylogenetic analysis recoversP. milneraeas a non-coelophysid coelophysoid theropod, representing the first-named unambiguous theropod from the Triassic of the UK. Recently, it has been suggested that Pant-y-ffynnon and other nearby Late Triassic to Early Jurassic fissure fill faunas might have been subjected to insular dwarfism. To test this hypothesis forP. milnerae, we performed an ancestral state reconstruction analysis of body size in early neotheropods. Although our results indicate that a reduced body size is autapomorphic forP. milnerae, some other coelophysoid taxa show a similar size reduction, and there is, therefore, ambiguous evidence to indicate that this species was subjected to dwarfism. Our analyses further indicate that, in contrast with averostran-line neotheropods, which increased in body size during the Triassic, coelophysoids underwent a small body size decrease early in their evolution.
Influence of environmental variation on spatial distribution and habitat-use in a benthic foraging marine predator
Authors: Speakman Cassie N. , Hoskins Andrew J. , Hindell Mark A. , Costa Daniel P. , Hartog Jason R. , Hobday Alistair J. , Arnould John P. Y.
Published: October 2021

The highly dynamic nature of the marine environment can have a substantial influence on the foraging behaviour and spatial distribution of marine predators, particularly in pelagic marine systems. However, knowledge of the susceptibility of benthic marine predators to environmental variability is limited. This study investigated the influence of local-scale environmental conditions and large-scale climate indices on the spatial distribution and habitat use in the benthic foraging Australian fur seal (Arctocephalus pusillus doriferus; AUFS). Female AUFS provisioning pups were instrumented with GPS or ARGOS platform terminal transmitter tags during the austral winters of 2001–2019 at Kanowna Island, south-eastern Australia. Individuals were most susceptible to changes in the Southern Oscillation Index that measures the strength of the El Niño Southern Oscillation, with larger foraging ranges, greater distances travelled and more dispersed movement associated with 1-yr lagged La Niña-like conditions. Additionally, the total distance travelled was negatively correlated with the current year sea surface temperature and 1-yr lagged Indian Ocean Dipole, and positively correlated with 1-yr lagged chlorophyll-aconcentration. These results suggest that environmental variation may influence the spatial distribution and availability of prey, even within benthic marine systems.
Chitosan propolis nanocomposite alone or in combination with apramycin: an alternative therapy for multidrug-resistant Salmonella Typhimurium in rabbits: in vitro and in vivo study
Authors: El-Sheikh Sawsan M. A. , Abd El-Alim Abd El-Alim F. , Ibrahim Hosny A. , Mobarez Elham A. , El-Sayed Walaa A. , Galal Azza A. A. , Awad Naglaa F. S.
Published: October 2021

Introduction. The emergence of multidrug-resistant Salmonella Typhimurium strains has increased the need for safe, alternative therapies from natural sources with antibacterial properties.

Hypothesis/Gap Statement. There are no published data regarding the use of chitosan propolis nanocomposite (CPNP) either alone or in combination with antibiotics as antimicrobials against S. Typhimurium, especially in Egypt.

Aim. This study evaluated the antibacterial activities of five antimicrobials [apramycin, propolis, chitosan nanoparticles (CNPs), chitosan propolis nanocomposite (CPNP) and CPNP +apramycin] against ten virulent and multidrug-resistant (MDR) S. Typhimurium field strains recovered from diarrheic rabbits through in vitro and in vivo study.

Methodology. The expression levels of three virulence genes of S. Typhimurium strains were determined by quantitative reverse-transcription PCR (RT-qPCR) after exposure to sub-inhibitory concentrations of apramycin, propolis, CNPs, CPNP alone, and CPNP +apramycin. Additionally, 90 New Zealand rabbits were divided into control and experimentally S. Typhimurium-infected groups. The infected rabbits were orally administered saline solution (infected–untreated); 10 mg apramycin/kg (infected–apramycin-treated); 50 mg propolis/kg (infected–propolis-treated); 15 mg CPNP/kg (infected–CPNP-treated) and 15 mg CPNP +10 mg apramycin/kg (infected–CPNP +apramycin-treated) for 5 days.

Results. The RT-qPCR analysis revealed different degrees of downregulation of all screened genes. Furthermore, the treatment of infected rabbits with CPNP or CPNP +apramycin significantly improved performance parameters, and total bacterial and

Salmonella

species counts, while also modulating both oxidative stress and altered liver and kidney parameters.

Conclusion. This work demonstrates the use of CPNP alone or in combination with apramycin in the treatment of S. Typhimurium in rabbits.
Induced antigen-binding polyreactivity in human serum IgA
Authors: Gorshkova Ekaterina N. , Lecerf Maxime , Astrakhantseva Irina V. , Vasilenko Ekaterina A. , Starkina Olga V. , Ilyukina Natalya A. , Dimitrova Petya A. , Dimitrov Jordan D. , Vassilev Tchavdar L.
Published: October 2021

Previous studies have shown that polyreactive antibodies play an important role in the frontline defense against the dissemination of pathogens in the pre-immune host. Interestingly, antigen-binding polyreactivity can not only be inherent, but also acquired post-translationally. The ability of individual monoclonal IgG and IgE antibodies to acquire polyreactivity following contact with various agents that destabilize protein structure (urea, low pH) or have pro-oxidative potential (heme, ferrous ions) has been studied in detail. However, to the best of our knowledge this property of human IgA has previously been described only cursorily. In the present study pooled human serum IgA and two human monoclonal IgA antibodies were exposed to buffers with acidic pH, to free heme or to ferrous ions, and the antigen-binding behavior of the native and modified IgA to viral and bacterial antigens were compared using immunoblot and ELISA. We observed a dose-dependent increase in reactivity to several bacterial extracts and to pure viral antigens. This newly described property of IgA may have therapeutic potential as has already been shown for pooled IgG with induced polyreactivity.
The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B5
Authors: Siddique Shahid , Radakovic Zoran S. , Hiltl Clarissa , Pellegrin Clement , Baum Thomas J. , Beasley Helen , Chitambo Oliver , Chopra Divykriti , Danchin Etienne G.J. , Grenier Eric , Habash Samer S. , Hasan M. Shamim , Helder Johannes , Hewezi Tarek , Holbein Julia , Holterman Martijn , Janakowski Sławomir , Koutsovoulos Georgios D. , Kranse Olaf P. , Lozano-Torres Jose L. , Maier Tom R. , Masonbrink Rick E. , Mendy Badou , Riemer Esther , Sobczak Mirosław , Sonawala Unnati , Sterken Mark G. , Thorpe Peter , van Steenbrugge Joris J.M. , Zahid Nageena , Grundler Florian , Eves-van den Akker Sebastian
Published: October 2021

Plant-parasitic nematodes are a major, and in some cases a dominant, threat to crop production in all agricultural systems. The relative scarcity of classical resistance genes highlights a pressing need to identify new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major stages of the interaction. This novel approach enabled the analysis of the hologenome of the infection site, to identify metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that the highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is critically important for parasitism. Knockout of either the plant-encoded or the now nematode-encoded steps in the pathway blocks parasitism. Our experiments establish a reference for cyst nematodes, use this platform to further our fundamental understanding of the evolution of plant-parasitism by nematodes, and show that understanding congruent differential expression of metabolic pathways represents a new way to find nematode susceptibility genes, and thereby, targets for future genome editing-mediated generation of nematode-resistant crops.
Diffusion MRI Metrics and their Relation to Dementia Severity: Effects of Harmonization Approaches
Authors: Thomopoulos Sophia I. , Nir Talia M. , Villalon-Reina Julio E. , Zavaliangos-Petropulu Artemis , Maiti Piyush , Zheng Hong , Nourollahimoghadam Elnaz , Jahanshad Neda , Thompson Paul M. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2021

Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to microstructural changes in the brain that occur with normal aging and Alzheimer’s disease (AD). There is much interest in which dMRI measures are most strongly correlated with clinical measures of AD severity, such as the clinical dementia rating (CDR), and biological processes that may be disrupted in AD, such as brain amyloid load measured using PET. Of these processes, some can be targeted using novel drugs. Since 2016, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has collected dMRI data from three scanner manufacturers across 58 sites using 7 different protocols that vary in angular resolution, scan duration, and in the number and distribution of diffusion-weighted gradients. Here, we assessed dMRI data from 730 of those individuals (447 cognitively normal controls, 214 with mild cognitive impairment, 69 with dementia; age: 74.1±7.9 years; 381 female/349 male). To harmonize data from different protocols, we applied ComBat, ComBat-GAM, and CovBat to dMRI metrics from 28 white matter regions of interest. We ranked all dMRI metrics in order of the strength of clinically relevant associations, and assessed how this depended on the harmonization methods employed. dMRI metrics were associated with age and clinical impairment, but also with amyloid positivity. All harmonization methods gave comparable results while enabling data integration across multiple scanners and protocols.
Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 Case Fatality Rate among Indian populations
Authors: Pandey Rudra Kumar , Srivastava Anshika , Singh Prajjval Pratap , Chaubey Gyaneshwer
Published: October 2021

SARS-CoV2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to enter the host cell through S protein priming by a serine protease, TMPRSS2. Variation in the TMPRSS2 gene may account for the difference in population disease susceptibility. The haplotype-based genetic sharing and structure of TMPRSS2 among global populations have not been studied so far. Therefore, in the present work, we used this approach with a focus on South Asia to study the haplotypes and their sharing among various populations worldwide. We have used next-generation sequencing data of 393 individuals and analysed the TMPRSS2 gene. Our analysis of genetic relatedness for this gene showed a closer affinity of South Asians with the West Eurasian populations therefore, host disease susceptibility and severity particularly in the context of TMPRSS2 will be more akin to West Eurasian instead of East Eurasian. This is in contrast to our prior study on ACE2 gene which shows South Asian haplotypes have a strong affinity towards West Eurasians. Thus ACE2 and TMPRSS2 have an antagonistic genetic relatedness among South Asians. We have also tested the SNP’s frequencies of this gene among various Indian state populations with respect to the case fatality rate. Interestingly, we found a significant positive association between the rs2070788 SNP (G Allele) and the case fatality rate in India. It has been shown that the GG genotype of rs2070788 allele tends to have a higher expression of TMPRSS2 in the lung compared to the AG and AA genotypes, thus it might play a vital part in determining differential disease vulnerability. We trust that this information will be useful in underscoring the role of the TMPRSS2 variant in COVID-19 susceptibility and using it as a biomarker may help to predict populations at risk.
Domain-selective BET inhibition attenuates transcriptional and behavioral responses to cocaine
Authors: Singh MB , Babigian CJ , Sartor GC
Published: October 2021

Epigenetic pharmacotherapies have emerged as a promising treatment option for substance use disorder (SUD) due to their ability to reverse maladaptive transcriptional and behavioral responses to drugs of abuse. In particular, inhibitors of bromodomain and extra terminal domain (BET) reader proteins have been shown to reduce cocaine- and opioid-seeking behaviors in rodents. However, only pan-BET inhibitors, small molecules that bind to both bromodomains (BD1 and BD2) with all BET proteins, have been investigated in animal models of SUD. Given the potential side effects associated with pan-BET inhibitors, safer and more selective strategies are needed to advance BET therapeutics as a potential treatment for SUD. Here, we show that RVX-208, a clinically tested, BD2-selective BET inhibitor, dose-dependently reduced cocaine conditioned place preference in male mice, similar to the pan-BET inhibitor JQ1. In other behavioral experiments, RVX-208 treatment did not alter distance traveled, anxiety-like behavior, or novel object recognition memory. At the transcriptional level, RVX-208 attenuated the expression of multiple cocaine-induced genes in the nucleus accumbens. RVX-208 produced a distinct transcriptional response in stimulated primary neurons compared to JQ1 but had little effect on gene expression in non-stimulated neurons. Together, these data indicate that targeting domain-specific BET mechanisms may be an effective and safer strategy to reduce cocaine-induced neurobehavioral adaptations.
Development of the Functional Connectome Topology in Adolescence: evidence from Topological Data Analysis
Authors: Gracia-Tabuenca Zeus , Díaz-Patiño Juan Carlos , Arelio Isaac , Moreno Martha Beatriz , Barrios Fernando A. , Alcauter Sarael
Published: October 2021

Adolescence is a crucial developmental period in terms of behavior and mental health. Therefore, understanding how the brain develops during this stage is a fundamental challenge for neuroscience. Recent studies have modelled the brain as a network or connectome, mainly applying measures from graph theory, showing a change in its functional organization such as an increase in its segregation and integration. Topological Data Analysis (TDA) complements such modelling by extracting high-dimensional features across the whole range of connectivity values, instead of exploring a fixed set of connections. This study enquiries into the developmental trajectories of such properties using a longitudinal sample of typically developing participants (N = 98; 53/45 F/M; 6.7-18.1 years), applying TDA into their functional connectomes. In addition, we explore the effect of puberty on the individual developmental trajectories. Results showed that compared to random networks, the adolescent brain is more segregated at the global level, but more densely connected at the local level. Furthermore, developmental effects showed nonlinear trajectories for the integration of the whole brain and fronto-parietal networks, with an inflection point and increasing trajectories after puberty onset. These results add to the insights in the development of the functional organization of the adolescent.

Significance Statement

Topological Data Analysis may be used to explore the topology of the brain along the whole range of connectivity values instead of selecting only a fixed set of connectivity thresholds. Here, we explored some properties of the topology of the brain functional connectome, and how they develop in adolescence. First, we show that developmental trajectories are nonlinear and better explained by the puberty status than chronological age, with an inflection point around the puberty onset. The greatest effect is the increase in functional integration for the whole brain, and particularly for the Fronto-Parietal Network when exploring functional subnetworks.