bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Polyphenol Concentration and Composition between Genetically Diverse Cacao (Theobroma cacao L.) Accessions Selected for High Yield
Authors: Lee Andrew H , Moore Amy , Tuzo Jessica , Neilson Andrew P , O'Keefe Sean F , Ogejo Jactone Arogo , Irish Brian , Stewart Amanda C
Published: June 2021

There is abundant evidence that consumption of cacao and dark chocolate promotes human health and that the main cacao components contributing positive health effects are polyphenols. The polyphenols in cacao bean constitute 12–18% dry weight of the whole bean and are predominantly catechins (37% w/w), procyanidins (58% w/w) and anthocyanins (4% w/w). Variation in cacao polyphenol composition and concentration can result from differences in genetic backgroud, agro‐environment and cultural practices. It is therefore important to consider several factors when selecting cacao seed (beans) for research investigating the mechanisms underlying its health benefits. In this study, dried unfermented seeds of five different cacao clones (TARS‐9, TARS‐14, TARS‐27, TARS‐30, TARS‐31) were obtained from USDA‐ARS Tropical Agriculture Research Station (TARS) located in Mayaguez, Puerto Rico. These clones were developed through controlled‐pollinated hybridization for improved agronomic performance, specifically high yield. Prior sensory evaluation of 65% chocolate made from these clones revealed that each conferred distinct profiles in bitterness. We thus hypothesized that differences in polyphenol profiles would exist between these clones. To test this hypothesis, total polyphenols, total flavan‐3ols, polyphenol extraction yield, and qualitative flavanol profile were compared between the five cacao clones. TARS‐27 had the lowest total polyphenol concentration (36 ± 1.2 mg gallic acid equivalents/g cacao bean) (mean ± STDEV), whereas TARS‐14 showed highest concentration (66 ± 4.7 mg gallic acid equivalents/g cacao bean). For total flavan‐3‐ols, a similar trend was observed; TARS‐27 showed the lowest concentration (42.3 ± 1.1 mg procyanidin B2 equivalents/g cacao bean) with TARS‐9 having the highest concentration (76.7 ± 4 mg procyanidin B2 equivalents/g cacao bean). Polyphenol extraction yield (cacao extract weight/cocoa bean weight) differed among clones ranging from 0.1–0.16. Qualitative flavanol profiles obtained using normal‐phase high‐performance liquid chromatography (HPLC) indicated that mean degree of polymerization (mDP) of polyphenols is likely similar between these clones. Further research is required to quantitatively determine mDP, and to identify and quantify individual polyphenols. In conclusion, these insights into the variability of polyphenol composition among genetically diverse cacao will help to inform targeted selection of cacao clones for future studies investigating the impact of cacao consumption on human health.

Support or Funding Information

Funding was provided, in part, by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture (NIFA), U.S. Department of Agriculture
Role of Serotonin Signaling in the Remodeling of Thioridazine‐Induced Craniofacial Deformities in Xenopus laevis Pre‐metamorphic Tadpoles
Authors: Familia Jerson Steve , Pinet Kaylinnette , McLaughlin Kelly A
Published: June 2021

Craniofacial abnormalities have recently been given special attention because of a rise in the number of microcephaly cases associated with the spread of the Zika virus. Microcephaly, however, is just one of various common craniofacial deformities that can occur in vertebrates during development. Since craniofacial development is well‐conserved across vertebrates, numerous model organisms can be utilized to study craniofacial development. To that end, our lab takes advantage of the tractable amphibian model system, Xenopus laevis. Our recent studies revealed pre‐metamorphic Xenopus tadpoles can self‐correct craniofacial defects induced by exposure to thioridazine HCl, a D2 dopamine receptor antagonist. The underlying molecular mechanism mediating this correction is unknown, and is thus the focus of our current work. Previously the Levin lab discovered that several developmental events, including the regulation of organ placement and cell movements during gastrulation, are mediated by neurotransmitters during development. Since the self‐correction of craniofacial defects includes both cell movement and tissue positioning, we are currently investigating whether the remodeling response is initiated and/or mediated by neurotransmitter‐dependent cellular pathways. Our current study utilized fluoxetine, a selective serotonin reuptake inhibitor, to block a candidate pathway throughout pre‐metamorphic stages in tadpoles. These experiments will help elucidate which signaling mechanism directs the correction of malformed craniofacial structures in tadpoles during pre‐metamorphic stages.

Support or Funding Information

The Paul G. Allen Frontiers Group, National Science Foundation, and American Society of Biochemistry and Molecular Biology
Cortactin controls morphological and electrophysiological properties during activity‐dependent synaptic plasticity at the Drosophila neuromuscular junction
Authors: Perez Marizabeth , Dominicci Carihann , Maldonado Carolina , Marie Bruno
Published: June 2021

In the nervous system, changes in activity that lead to modifications in synaptic structure and function are referred to as synaptic plasticity and are thought to be the basis of learning and memory. Such modifications can be studied at the Drosophila neuromuscular junction (NMJ); a model used to decipher the molecular mechanisms underlying activity‐dependent synaptic plasticity. Recent work has shown that, after repeated stimulations, de novo synaptic structures form at the NMJ and an increase in the frequency of spontaneous release occurs. While the secreted molecule Wingless (Wg)/Wnt was shown to underlie the structural and electrophysiological changes during activity‐dependent plasticity at the NMJ, a challenge remains to understand how this signal mediates the cellular changes that lead to plasticity.

In this work, we investigate the role of the actin regulator Cortactin (Cttn) in activity‐dependent synaptic plasticity. With confocal microscopy, we show that Cttn is present at the NMJ, pre and postsynaptically. Also, we show that the synaptic structures that are formed during synaptic plasticity are dependent on presynaptic Cttn expression. In addition, our electrophysiological recordings show that Cttn‐deficient NMJs have a significant reduction in the frequency of spontaneous release. Such reduction can only be rescued by the presynaptic expression of Cttn, which suggests that the neuronal expression of Cttn is necessary for maintaining the rate of spontaneous vesicle fusion at the NMJ. Moreover, presynaptic Cttn is required for the potentiation of spontaneous release that occurs after activity‐dependent synaptic plasticity. Indeed, there is no potentiation of spontaneous release in Cttn mutants and in NMJs depleted of presynaptic Cttn. However, this potentiation is achieved if Cttn is expressed presynaptically in Cttn mutants, or if Cttn is removed only postsynaptically. We argue that presynaptic Cttn is responsible for the structural and/or functional changes affecting active zones during activity‐dependent synaptic plasticity. Overall, our findings suggest that Cttn is an important regulator of structural and physiological synaptic properties in response to activity.

Support or Funding Information

This work was supported by the NIGMS 1P20GM103642 grant to BM and MP; NINDS SC2NS077924 and NSF HRD‐1137725 to BM. Work supported by NIMHD 8G12‐MD007600 RCMI grant. CD and CM received support from NIGMS RISE grant R25GM061838. MP received support from NIGMS RISE grant R25GM06115115.
Insulin signaling during immune challenges: Friend or foe?
Authors: Cambron Lizzette D , Greenlee Kendra J
Published: June 2021

One commonality between humans, dogs, and even insects, is that when faced with an illness all three will cease eating. This response across varying taxa is called sickness‐induced anorexia (SIA). SIA is hypothesized to be an energy reallocation toward immune function. However, the mechanism mediating the response, and the signal telling the body to stop eating is still unknown. Along with this response, insulin signaling is conserved between vertebrate and invertebrates. Because insulin signaling plays a role in regulating many physiology processes such as metabolism, development, and reproduction, this experiment aimed to investigate the role of insulin signaling in immune responses, specifically that of SIA, using the tobacco hornworm, Manduca sexta. In the beginning of the last larval stage, caterpillars were injected with either vehicle (PBS) or Escherichia coli to initiate an immune challenge. Then, insulin signaling was either inhibited by wortmannin, a covalent inhibitor of phosphoinositide 3‐kinases, or increased with exogenous bovine insulin. Growth, feeding, development, and fecal pellet measurements were taken daily until prepupation, indicated by the appearance of the dorsal vessel. Caterpillars that were injected with E. coli exhibited SIA, as previously shown. We predicted that caterpillars lacking insulin signaling would still exhibit SIA in response to E. coli, however, in this and previous studies, wortmannin showed contradictory results, suggesting that wortmannin may be activating other pathways or incompletely inhibiting insulin signaling. Interestingly, SIA was completely blocked in caterpillars that received extra insulin, supporting the hypothesis that insulin signaling mediates feeding. Further studies are needed to discover the mechanism tying insulin signaling to immunity. Elucidating the mechanism behind SIA will lead to a better understanding of how insulin signaling and the immune system intertwine, improving how we treat diabetics which are more susceptible to contracting infections.

Support or Funding Information

This research was funded in part, by grants from the National Science Foundation (NSF IOS‐0953297 to KJG) and the NSF Graduate Research Fellowships Program.
Reversibly Constraining The Human U1 snRNP And The Spliceosome To A Pre‐mRNA Via An Engineered Site‐specific Disulfide Bond
Authors: McCarthy Patrick , Garside Erin , MacMillan Andrew , Krummel Daniel Pomeranz
Published: June 2021

Pre‐messenger RNA splicing of protein‐coding RNA transcripts governs metazoan development. Pre‐mRNA splicing is catalyzed by the dynamic mega‐dalton spliceosome, formed by an ordered assembly of five U snRNPs (U1, U2, U4, U5 and U6 snRNPs) and non‐U snRNP proteins onto a pre‐mRNA substrate. The U snRNPs bind to and separate from the pre‐messenger RNA at key stages in the pre‐catalytic assembly of the spliceosome. The spliceosome assembly cycle is initiated with the recognition of the pre‐mRNA substrate 5′ splice site by the U1 snRNP which remains associated at this site during the recruitment of other U snRNPs. The U1 snRNP as well as the U4 snRNP and several other factors are subsequently displaced from their pre‐mRNA binding sites during the formation of a catalytic spliceosome. The mechanism, order, and importance of these displacement events is poorly understood, in part due to the challenges presented by the spliceosome's large size, dynamics, and crude source of material. In order to investigate the pre‐catalytic to catalytic transition undergone by the spliceosome, we have engineered a disulfide bond between a rationally designed U1‐C cysteine residue and a site‐specific thiol‐modified backbone of a pre‐mRNA substrate, allowing us to establish a reversible disulfide crosslink between a pre‐mRNA and the U1‐C protein alone as well as in the context of the U1 snRNP. This strategy will allow for a mechanistic elucidation of the critical pre‐catalytic to catalytic transition in spliceosome assembly, including examination of a possible sequential displacement of pre‐catalytic complexes in the activation of the spliceosome.

Support or Funding Information

National Science Foundation Award No. 1157892
Comparison of equipotent doses of intrathecal hyperbaric prilocaine 2% and hyperbaric bupivacaine 0.5% for elective caesarean section
Authors: Goffard Philippe , Leloup Renaud , Vercruysse Yoann , Fils Jean-François , Gautier Philippe Emmanuel , Kapessidou Yota
Published: June 2021

BACKGROUND

Elective caesarean section is performed mainly under spinal anaesthesia using hyperbaric bupivacaine combined with opioids. Despite rapid onset, good quality anaesthesia, bupivacaine provides a long duration of motor block and is related to maternal hypotension. Current policies appeal for implementation of enhanced recovery procedures after caesarean section. Hyperbaric prilocaine is an intermediate-acting local anaesthetic known for its efficacy in ambulatory surgery. Evidence on the clinical relevance of intrathecal prilocaine use for caesarean section is currently lacking.

OBJECTIVES

We aimed to investigate whether hyperbaric prilocaine would offer a shorter motor block and recovery than bupivacaine, when comparing equipotent doses. We also assessed the characteristics of sensory block, maternal haemodynamics and side effects for both mother and newborn.

DESIGN

Prospective, randomised, double-blind, controlled, two-centre, clinical trial.

SETTING

One university teaching hospital and one general teaching hospital in Brussels, Belgium.

PATIENTS

American Society of Anesthesiologists’ physical status 2 parturients (n = 40) undergoing caesarean section under spinal anaesthesia.

INTERVENTIONS

Patients were randomly assigned to receive spinal anaesthesia using hyperbaric prilocaine 50 mg or hyperbaric bupivacaine 10 mg, both given with sufentanil 2.5 μg and morphine 100 μg. An epidural catheter was introduced as a backup in case of failure.

MAIN OUTCOMES

The primary outcome was the motor block regression (modified Bromage scale 1 to 6). Secondary outcomes included sensory block characteristics, first unassisted ambulation, maternal side effects, newborns’ parameters and overall satisfaction.

RESULTS

Median [IQR] motor block was significantly shorter in the hyperbaric prilocaine group (110 [104 to 150] min versus 175 [135 to 189] min, P = 0.001). First unassisted ambulation was achieved earlier after prilocaine (204.5 [177 to 246.5] min versus 314 [209.25 to 400] min, P = 0.007), and the incidence of maternal hypotension was significantly higher with bupivacaine (P = 0.033). No supplementary epidural analgesia was needed.

CONCLUSION

Prilocaine provides shorter motor block, faster recovery and better haemodynamic stability than bupivacaine while offering equivalent surgical anaesthesia.

TRIAL REGISTRATION

Clinicaltrials.gov: NCT02973048, EudraCT: 2016-003010-26.
Isolated diastolic vs. systolic hypertension phenotypes and outcomes: prospective cohort of newly diagnosed individuals with hypertension
Authors: Thomopoulos Costas , Andrikou Ioannis , Konstantinidis Dimitris , Iliakis Panagiotis , Kalos Theodoros , Polyzos Dimitrios , Drogkaris Sotirios , Siafi Eirini , Tousoulis Dimitrios , Stergiou George S. , Tsioufis Costas
Published: June 2021

Aims:

To evaluate whether different hypertension phenotypes, namely, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systolic/diastolic hypertension (SDH) have a differential outcome effect by clinic and ambulatory blood pressure (BP) measurements.

Methods:

We prospectively evaluated in 569 never-treated patients with sustained hypertension (age 52.6 ± 11.6 years; men 55%; clinic BP 150 ± 15/95.5 ± 10 mmHg, systolic/diastolic; 24-h ambulatory BP 128.9 ± 12.6/80.6 ± 9.7) the incidence of major cardiovascular (CV) events within 5 years, after adjustment for confounders, including the rate of BP control and the weighted follow-up BP.

Results:

All participants received antihypertensive drug treatment (mean number of drugs 1.9 ± 1.1; follow-up visits 4.6/patient). Average clinic BP achieved during follow-up was 136 ± 12.6/83.9 ± 9.4 mmHg, with 39% of participants having clinic BP less than 140/90 mmHg in at least 75% of their visits, and 24% in 25–75% of visits. Prevalence of hypertension phenotypes defined using BP differed from that using ambulatory BP, whereas integration of both BP measurements reclassified the initial phenotype to another in 18% of participants. Although, no differential outcome effect was observed between clinic IDH and SDH assessed using clinic or ambulatory BP measurements, clinic BP-based ISH was associated with a higher outcome incidence than the IDH and SDH phenotypes (hazard ratio 4.8, 95% confidence interval 1.4–17.0, P = 0.015). ISH diagnosed by integration of clinic and ambulatory BP, also increased the outcome (hazard ratio 4.0, 95% confidence interval 1.0–15.6, P = 0.046).

Conclusion:

In hypertensive patients at low/moderate CV risk, IDH and SDH phenotypes defined by clinic BP measurements, equally determined CV events but to a lower extent compared with ISH.
Current state of antigen-specific immunotherapy for type 1 diabetes
Authors: Kreiner Frederik Flindt , von Scholten Bernt Johan , Coppieters Ken , von Herrath Matthias
Published: June 2021

Purpose of review

Update on antigen-specific immunotherapy (ASIT) in type 1 diabetes (T1D) with focus on deoxyribonucleic acid (DNA)-induced immunization and the current obstacles to further research and clinical realization.

Recent findings

In T1D, immune system imbalances together with malfunctioning islet-specific processes cause autoreactive immune cells to destroy beta cells in the islets. ASIT may restore self-tolerance; however, the approach has yet to fully meet its promise and may require co-administration of antigen (preproinsulin) and suitable immune response modifiers.

A self-tolerant immune system may be regained using ASIT where T effector cells are repressed and/or T regulatory cells are induced. Administration of exogenous antigens has been safe in T1D. Conversely, adequate and lasting beta cell preservation has yet to be tested in sufficiently large clinical trials in suitable patients and may require targeting of multiple parts of the immunopathophysiology using combination therapies. DNA-based induction of native antigen expression to ensure important posttranscriptional modifications and presentation to the immune system together with tolerance-enhancing immune response modifiers (i.e., cytokines) may be more efficacious than exogenous antigens given alone. Progress is limited mainly by the scarcity of validated biomarkers to track the effects of ASIT in T1D.
Acromegaly: achieving timely diagnosis and improving outcomes by personalized care
Authors: Ioachimescu Adriana G.
Published: June 2021

Purpose of review

Discuss recent literature regarding clinical manifestations and comorbidities in acromegaly, with focus on early diagnosis and customized care.

Recent findings

The mean interval between onset of clinical manifestations and diagnosis is currently 3–5 years. Women, especially younger than 50 years of age, experience longer delays, have lower insulin-like growth factor 1 (IGF-1) levels and larger tumors than men. Development of comorbidities usually precedes the diagnosis and is influenced by age, sex, and biochemical disease activity. Comorbidities other than irreversible osteoarticular structural changes usually improve after acromegaly treatment. In patients with diabetes, the course of hyperglycemia not only depends on biochemical control but also on specific acromegaly therapies. Quality of life is influenced by sex, as well as by acromegaly symptoms, biochemical activity, and treatment. Quality of life remains lower than general population despite biochemical remission.

Early diagnosis can be achieved by suspecting acromegaly based on suggestive clinical scenarios rather than obvious changes in appearance. Personalized care entails a proactive multidisciplinary approach to identify and treat comorbidities while carefully monitoring the effects of acromegaly treatment.
Digital dermatoses: skin disorders engendered by social media in tweens and teens
Authors: Young Trevor K. , Oza Vikash S.
Published: June 2021

Purpose of review

Photograph-based social media use among children and adolescents has skyrocketed over the past decade, raising concerns about the implications for self-confidence and behavior in this population. Social media ‘challenges’ encourage participants to complete potentially dangerous tasks while sharing their completion of the tasks on social media. Many of these challenges affect the skin and lead to recognizable findings on physical examination. This review discusses the history of prominent social media challenges and their effects on the skin. Attention is also given to the effects of social media trends on self-confidence and body image in children and adolescents.

Recent findings

Over the past several years, there have been several notable social media trends that can harm the skin. These include the Kylie Jenner lip challenge, salt and ice challenge, deodorant challenge, eraser challenge, fire challenge, and hot water challenge. Participation in these challenges can cause morbidity in children and adolescent that should be recognized by clinicians.

Social media has become an important platform for communication and self-expression among children and adolescents. Pediatricians should remain aware of social trends in this age group and look out for cutaneous findings that may signal dangerous behavior on social media.
Incident Management in Health Care
Authors: Espin Sherry , D'Arpino Maryanne , Indar Alyssa , Gross Marketa
Published: June 2021

Background:

Nearly 10% of patients experience a harmful patient safety incident in the hospital setting. Current evidence focuses on incident reporting, whereas little is known about how incidents are managed within organizations.

Purpose:

The aim of this study was to explore processes, tools, and resources for incident management in Canadian health care organizations.

Methods:

Qualitative focus groups were conducted with key stakeholders, representing clinicians, managers, executives, governors, patients, and families (n = 45).

Results:

Qualitative data were thematically analyzed and presented as 3 themes: (1) variations in incident reporting and management; (2) simplification of the incident management process; and (3) need for leadership to support just culture and redefine harm.

Conclusion:

The study findings support and inform efforts to create a patient safety culture in Canadian and international health care organizations. There is a need to develop a standardized, accessible incident reporting and management system for use across health care sectors to promote continuous learning and improvement about patient safety.
Survival following screening and preemptive antifungal therapy for subclinical cryptococcal disease in advanced HIV infection
Authors: Makadzange Tariro Azure , Hlupeni Admire , Machekano Rhoderick , Boyd Kathryn , Mtisi Takudzwa , Nyamayaro Primrose , Ross Christine , Vallabhaneni Snighdha , Balachandra Shirish , Chonzi Prosper , Ndhlovu Chiratidzo Ellen
Published: June 2021

Objectives:

Our study's primary objective was to compare 1-year survival rates between serum cryptococcal antigen (sCrAg)-positive and sCrAg-negative HIV-positive individuals with CD4+ cell counts less than 100 cells/μl without symptoms of meningitis in Zimbabwe.

Design:

This was a prospective cohort study.

Methods:

Participants were enrolled as either sCrAg-positive or sCrAg-negative and followed up for 52 weeks or less, with death as the outcome. Lumbar punctures were recommended to all sCrAg-positives and inpatient management with intravenous amphotericin B and high-dose fluconazole was recommended to those with disseminated Cryptococcus. Antiretroviral therapy was initiated immediately in sCrAg-negatives and after at least 4 weeks following initiation of antifungals in sCrAg-positives. Multivariable logistic regression models were used to determine risk factors for mortality.

Results:

We enrolled 1320 participants and 130 (9.8%) were sCrAg positive, with a median sCrAg titre of 1 : 20. Sixty-six (50.8%) sCrAg-positives had lumbar punctures and 16.7% (11/66) had central nervous system (CNS) dissemination. Cryptococcal blood cultures were performed in 129 sCrAg-positives, with 10 (7.8%) being positive. One-year (48–52 weeks) survival rates were 83.9 and 76.1% in sCrAg-negatives and sCrAg-positives, respectively, P = 0.011. Factors associated with increased mortality were a positive sCrAg, CD4+ cell count less than 50 cells/μl and having presumptive tuberculosis (TB) symptoms.

Conclusion:

Our study reports a high prevalence of subclinical cryptococcal antigenemia and reiterates the importance of TB and a positive sCrAg as risk factors for mortality in advanced HIV disease (AHD). Therefore, TB and sCrAg screening remains a crucial component of AHD package, hence it should always be part of the comprehensive clinical evaluation in AHD patients.
High-risk human papilloma virus, precancerous lesions and cancer in anal condylomas
Authors: Albuquerque Andreia , Cappello Carmelina , Stirrup Oliver
Published: June 2021

Introduction:

Anal condylomas are associated with human papillomavirus (HPV) infection and are a risk factor for anal squamous cell carcinoma (SCC).

Objective:

To conduct a meta-analysis evaluating the prevalence of anal high-risk HPV, high-grade squamous intraepithelial lesions (HSIL) and SCC in patients with condylomas. The standardized incidence ratio (SIR) and the incidence rate of anal SCC were also calculated.

Methods:

Three electronic databases were searched until April 2020. Meta-analyses were performed using random effects models.

Results:

Pooled prevalence estimate of high-risk HPV (HR-HPV) in anal condylomas was 40.2% (21.0–63.1) in immunocompromised and 16.4% (10.7–24.3) in nonimmunocompromised patients, with an odds ratio (OR) of 3.79 (1.51–9.52, P = 0.005) for immunocompromised patients. HR-HPV in condylomas with HSIL was 73.8% (39.1–92.5) and in non-HSIL cases was 17.7% (9.6–30.2), corresponding to an OR of 12.33 (2.97–51.21, P = 0.001) for those with HSIL. The prevalence of HSIL in condylomas was 24.0% (16.4–33.7) in immunocompromised and 11.8% (7.2–18.8) in nonimmunocompromised patients, with an OR of 2.51 (1.72–3.65, P < 0.001) for immunocompromised patients. The overall prevalence of anal SCC in anal condylomas was 0.3% (0.0–1.7). The SIR of anal SCC was 10.7 (8.5–13.5), 20.1 (14.4–28.2) in men and 7.7 (5.6–10.5) in women. The overall incidence rate of anal SCC was 6.5 per 100 000 person-years (3.6–11.7), 12.7 (9.1–17.8) in men and 4.7 (1.7–13) in women.

Conclusion:

Patients with a history of anal condylomas have a high risk of anal SCC, especially men. The prevalence of HR-HPV and HSIL in condylomas from immunocompromised patients is high. This information can change patient follow-up and treatment.
Three-Dimensional Magnetic Resonance Fingerprinting in Neonates
Authors: Yu Nali , Kim Jee Young , Han Dongyeob , Kim So Young , Lee Hye Mi , Kim Dong-Hyun , Kim Hyun Gi
Published: June 2021

Objectives

Magnetic resonance fingerprinting (MRF) allows the simultaneous measurement of multiple tissue properties in a single acquisition. Three-dimensional (3D) MRF with high spatial resolution can be used for neonatal brain imaging. The aim of this study is to apply 3D MRF to neonates and show regional differences and maturation in the brain.

Materials and Methods

In this prospective study, 3D MRF using hybrid radial-interleaved acquisition was performed on phantoms and neonates from December 2019 to October 2020. For the reconstruction of 3D MRF, singular value decomposition was applied to reduce reconstruction time, and the iterative reconstruction technique was applied to improve image quality. The accuracies of T1 and T2 values derived from 3D MRF were evaluated in a phantom experiment. Regional T1 and T2 values were obtained from neonates' brain T1 and T2 maps derived from 3D MRF. Regional T1 and T2 values were compared, and their changes according to corrected gestational age were evaluated.

Results

The acquisition time for 3D MRF with a spatial resolution of 0.7 × 0.7 × 2 mm3 was less than 5 minutes. The phantom study showed high correlation between T1 and T2 values derived from 3D MRF and those from conventional spin echo sequences (T1, R
2 = 0.998, P < 0.001; T2, R
2 = 0.998, P < 0.001). Three-dimensional MRF was performed in 25 neonates (15 boys, 10 girls; median corrected gestational age, 263 days; interquartile range, 10 days). In neonates, T1 and T2 values differed in the frontal (median [interquartile range], 2785 [2684–2888] milliseconds and 189.8 [176.7–222.9] milliseconds), parietal (2849 [2741–2950] milliseconds and 191.6 [167.5–232.9] milliseconds), and occipital white matter (2621 [2513–2722] milliseconds and 162.9 [143.5–186.1] milliseconds), showing lower values in occipital white matter (P < 0.001). Regional T1 values showed a negative relationship with corrected gestational age (coefficient, −0.775 to −0.480; P < 0.05).

Conclusions

Fast and high spatial resolution 3D MRF was applied to neonates. T1 and T2 maps derived from 3D MRF enabled the quantification of regional differences and maturation in the neonatal brain.
A Simple Technique to Correct Lumpectomy Deformities Using Free Nipple Grafting
Authors: Van Vliet Austin , Dayicioglu Deniz
Published: June 2021

Background

Lumpectomy followed by radiation can lead to severe breast asymmetry. Many surgeons are hesitant to perform traditional mastopexies on irradiated breasts due to increased complication rates. An alternative approach to achieve breast symmetry is presented. This technique consists of free nipple-areola complex (NAC) grafting of the irradiated breast to a higher position and primary closure of the donor site, in an appropriate fashion without undermining, followed by a formal mastopexy of the nonradiated breast.

Objective

To evaluate the outcomes of free NAC grafting, used as an alternative method to achieve breast symmetry, in patients who underwent lumpectomy with radiation.

Methods

A case series of 5 patients who underwent breast revision using this technique, performed by a single surgeon from 2017 to 2019 (n = 5), is presented.

Patient Demographics

All patients had history of lumpectomy followed by radiation therapy. The average age was 59.2 years, average BMI was 33.0. Three of 5 patients had a significant smoking history. The average time between radiation and surgery was 5.9 years.

Results

The average operating time was 141.8 minutes. The average follow-up period was 5.8 months. Two (40%) of the free NAC grafts were complicated by hypopigmentation of the reconstructed NAC. No major complications were reported, and no patients required return to the operating room. All patients had successful outcomes with improved breast symmetry.

Conclusions

Free NAC grafting of irradiated breasts and contralateral mastopexy may be a reliable alternative to achieve breast symmetry, with a less invasive approach, in patients who underwent lumpectomy and radiation.
The Case for Onlay Biologic Mesh in Abdominal Wall Reconstruction Using Progressive Tension Suture Fixation
Authors: Lindsey John T. , Boyd Carter J. , Davis Claire , Wilson John , Kurapati Srikanth , de la Torre Jorge I.
Published: June 2021

Background

After many years of debate, underlay and sublay placement of mesh slowly emerged as the standard of care in abdominal wall reconstruction because of lower hernia recurrence rates. However, onlay has the advantages of being faster, less invasive, and technically easier compared with underlay and sublay. Therefore, if a similar recurrence could be achieved, then onlay should be a consideration. In this study, we present a new onlay method using multipoint progressive tension suture fixation.

Methods

This was a retrospective chart review of patients who underwent abdominal wall reconstruction from 2012 to 2019. Inclusion criteria included onlay mesh placement and at least 1 year of follow-up. The core principles of the surgical technique are establishing myofascial continuity by component separation and reinforcing the repair with onlay mesh that is fixated with multipoint progressive tension sutures.

Results

The number of patients after exclusions was 59, and the average body mass index was 32.52 ± 6.44 kg/m2. More than half (62.7%) of patients had a history of hypertension, 95% had at least 1 prior abdominal/pelvic surgery, and 61% had at least 1 prior hernia repair. Postoperative complications included 20.3% of patients requiring drainage of a fluid collection in the clinic setting, and 29.3% of patients requiring return to the operating room for any reason (including superficial wound debridement). The average defect size was 231.88 ± 195.86 cm2, the mean follow-up was 3.11 ± 1.83 years, and the recurrence rate was 5.1%.

Conclusions

We report a hernia recurrence rate of 5.1% in a high-risk population with complex defects at a mean of 3.1 years of follow-up using onlay mesh fixated with multipoint progressive tension sutures. This recurrence rate is similar to that reported for both underlay and sublay techniques. However, the onlay approach is technically easier, faster, and less invasive compared with underlay and sublay techniques, which may translate into wider reproducibility, lower costs, and improved patient safety.
A Core Outcome Set for Seamless, Standardized Evaluation of Innovative Surgical Procedures and Devices (COHESIVE)
Authors: Avery Kerry N.L. , Wilson Nicholas , Macefield Rhiannon , McNair Angus , Hoffmann Christin , Blazeby Jane M. , Potter Shelley ,   On behalf of the Core Outcomes for early pHasE Surgical Innovation and deVicEs (COHESIVE) study steering group
Published: June 2021

Objective:

To develop a COS, an agreed minimum set of outcomes to measure and report in all studies evaluating the introduction and evaluation of novel surgical techniques.

Summary of Background Data:

Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm.

Methods:

(I) Generation of a list of outcome domains from published innovation-specific literature, policy/regulatory body documents, and surgeon interviews; (II) Prioritization of identified outcome domains using an international, multi-stakeholder Delphi survey; (III) Consensus meeting to agree the final COS. Participants were international stakeholders, including patients/public, surgeons, device manufacturers, regulators, trialists, methodologists, and journal editors.

Results:

A total of 7972 verbatim outcomes were identified, categorized into 32 domains, and formatted into survey items/questions. Four hundred ten international participants (220 professionals, 190 patients/public) completed at least one round 1 survey item, of which 153 (69.5%) professionals and 116 (61.1%) patients completed at least one round 2 item. Twelve outcomes were scored “consensus in” (“very important” by ≥70% of patients and professionals) and 20 “no consensus.” A consensus meeting, involving

context: modifications, unexpected disadvantages, device problems, technical procedure completion success, patients’ experience relating to the procedure being innovative, surgeons’/operators’ experience. Other domains relate to intended benefits, whether the overall desired effect was achieved and expected disadvantages.

Conclusions:

The COS is recommended for use in all studies before definitive randomized controlled trial evaluation to promote safe, transparent, and efficient surgical innovation.
SIRT2 inhibition exacerbates p53-mediated ferroptosis in mice following experimental traumatic brain injury
Authors: Gao Jinpeng , Li Yunfeng , Song Ran
Published: June 2021

Objective

Ferroptosis plays an important role in traumatic brain injury (TBI). The p53 protein is a major mediator of ferroptosis. However, the role of p53-mediated ferroptosis in TBI has not been studied. Sirtuin 2 (SIRT2) exerts a protective effects role in TBI, although the underlying mechanism of this protection remains unclear. In the present study, we tested the hypothesis that that SIRT2 mitigates TBI by regulating p53-mediated ferroptosis.

Methods and results

To model TBI in mice, we used the controlled cortical impact (CCI) injury method. We found that ferroptosis was significantly activated by CCI, and peaked 3 days following CCI, as evidenced by upregulation of GPX4 and SLC7A11, increased content of decreases glutathione, lipid peroxidation, malondialdehyde and ferrous ion. Inhibition of ferroptosis significantly alleviated neurological indications and brain edema. In addition, knockout of p53 significantly blocked ferroptosis following CCI. Furthermore, we found that inhibition of SIRT2 upregulated the acetylation of p53, as well as p53 expression, and exacerbated ferroptosis following CCI. Interestingly, knockout of p53 rescued the SIRT2 inhibition-induced exacerbation of ferroptosis.

Conclusions

These findings indicate that p53-mediated ferroptosis contributes to the pathogenesis of TBI. Furthermore, we demonstrate that SIRT2 exerts a neuroprotective effect against TBI by suppressing p53-mediated ferroptosis.
MicroRNA-488 inhibits neural inflammation and apoptosis in spinal cord injury through restraint on the HMGB1/TLR4/NF-κB signaling pathway
Authors: Niu Feng , Pan Shan
Published: June 2021

Objectives

Secondary spinal cord injury (SCI), a reversible pathological change, involves neural inflammation and apoptosis. This study explored how microRNA (miR)-488, an inflammatory regulator as reported affected secondary SCI.

Methods

In vivo, Wistar rats were clipped on the spinal cord for SCI induction. In vitro, PC-12 cells were treated with lipopolysaccharide (LPS) to induce cell injuries to mimic the environment during the secondary SCI. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The levels of inflammation-related factors (interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α) in the serum and PC-12 cells were determined by ELISA. The expressions of miR-488, high mobility group box 1 (HMGB1), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, toll-like receptor 4 (TLR4), phosphorylated (p)-p65 and total-p65 in rat spinal cord or PC-12 cells were analyzed by quantitative reverse transcription PCR or western blot.

Results

After SCI induction, rats exhibited low Basso–Beattie–Bresnahan scores, promoted the release of inflammation-related factors and downregulated miR-488. LPS treatment decreased cell viability, enhanced apoptosis and downregulated miR-488. Upregulating miR-488 neutralized LPS-induced releases of inflammation-related factors and expressions of Bax and cleaved caspase-3 and counteracted LPS-induced inhibition on Bcl-2 expression. MiR-488 directly targeted HMGB1 and miR-488 mimic decreased LPS-induced HMGB1 expression. Overexpressing HMGB1 counteracted miR-488 mimic-induced decreases in the expressions of TLR4 and p-p65 and the ratio of p-p65 to Total-p65 in LPS-treated PC-12 cells.

Conclusion

MiR-488 inhibited neural inflammation and apoptosis in SCI via its binding with HMGB1-mediated restraint on the TLR4/NF-κB signaling pathway.
The effect of thedoublesexgene in body colour masculinization of the damselflyIschnura senegalensis
Authors: Takahashi Michihiko , Okude Genta , Futahashi Ryo , Takahashi Yuma , Kawata Masakado
Published: June 2021

Odonata species display a remarkable diversity of colour patterns, including intrasexual polymorphisms. In the damselfly (Ischnura senegalensis), the expression of a sex-determining transcription factor, thedoublesex(Isdsx) gene is reportedly associated with female colour polymorphism (CP) (gynomorph for female-specific colour and andromorph for male-mimicking colour). Here, the function ofIsdsxin thoracic coloration was investigated by electroporation-mediated RNA interference (RNAi). RNAi of theIsdsxcommon region in males and andromorphic females reduced melanization and thus changed the colour pattern into that of gynomorphic females, while the gynomorphic colour pattern was not affected. By contrast, RNAi against theIsdsxlong isoform produced no changes, suggesting that theIsdsxshort isoform is important for body colour masculinization in both males and andromorphic females. When examining the expression levels of five genes with differences between sexes and female morphs, two melanin-suppressing genes,blackandebony, were expressed at higher levels in theIsdsxRNAi body area than a control area. Therefore, theIsdsxshort isoform may induce thoracic colour differentiation by suppressingblackandebony, thereby generating female CP inI. senegalensis.These findings contribute to the understanding of the molecular and evolutionary mechanisms underlying female CP in Odonata.
Pervasive decline of subtropical aquatic insects over 20 years driven by water transparency, non-native fish and stoichiometric imbalance
Authors: Romero Gustavo Q. , Moi Dieison A. , Nash Liam N. , Antiqueira Pablo A. P. , Mormul Roger P. , Kratina Pavel
Published: June 2021

Insect abundance and diversity are declining worldwide. Although recent research found freshwater insect populations to be increasing in some regions, there is a critical lack of data from tropical and subtropical regions. Here, we examine a 20-year monitoring dataset of freshwater insects from a subtropical floodplain comprising a diverse suite of rivers, shallow lakes, channels and backwaters. We found a pervasive decline in abundance of all major insect orders (Odonata, Ephemeroptera, Trichoptera, Megaloptera, Coleoptera, Hemiptera and Diptera) and families, regardless of their functional role or body size. Similarly, Chironomidae species richness decreased over the same time period. The main drivers of this pervasive insect decline were increased concurrent invasions of non-native insectivorous fish, water transparency and changes to water stoichiometry (i.e. N : P ratios) over time. All these drivers represent human impacts caused by reservoir construction. This work sheds light on the importance of long-term studies for a deeper understanding of human-induced impacts on aquatic insects. We highlight that extended anthropogenic impact monitoring and mitigation actions are pivotal in maintaining freshwater ecosystem integrity.
Ergonomic risk factors and Work-Related Musculoskeletal Disorders among Fireworks workers in West Bengal, India: A cross sectional study
Authors: Laskar Payel , Ganguly Subhadeep , Md Hossain Zakir
Published: June 2021

Objective

Fireworks industries are very old, unorganized cottage industries in West Bengal mainly confined in South 24 Parganas. The present investigation was intended to investigate the prevalence of work-related musculoskeletal disorders among the workers and to identify the causative factors behind it.

Method

In this present study, 152 male fireworks workers from different age groups and 100 control subjects were investigated. Modified Nordic questionnaire were used to identify the region wise disorders. Hand Grip strength of both groups were also estimated.

Result

Among the fireworks workers posture related musculoskeletal disorders were severely observed in the lower back which was aggravated with the advancement of age and working experience. Pain and stiffness were also reported in neck, upper back, wrist, elbow, knee and ankle. Lower back rest with support at lumber region was strongly recommended.

Conclusion

After analysis of ergonomic factors and results, it can be concluded that the fire workers who are working with awkward postures have high risk of developing WMSDs specially affecting the upper limbs and both upper and lower back.
HistoClean: Open-source Software for Histological Image Pre-processing and Augmentation to Improve Development of Robust Convolutional Neural Networks
Authors: McCombe Kris D. , Craig Stephanie G. , Pulsawatdi Amélie Viratham , Quezada-Marín Javier I. , Hagan Matthew , Rajendran Simon , Humphries Matthew P. , Bingham Victoria , Salto-Tellez Manuel , Gault Richard , James Jacqueline A.
Published: June 2021

The growth of digital pathology over the past decade has opened new research pathways and insights in cancer prediction and prognosis. In particular, there has been a surge in deep learning and computer vision techniques to analyse digital images. Common practice in this area is to use image pre-processing and augmentation to prevent bias and overfitting, creating a more robust deep learning model. Herein we introduce HistoClean; user-friendly, graphical user interface that brings together multiple image processing modules into one easy to use toolkit. In this study, we utilise HistoClean to pre-process images for a simple convolutional neural network used to detect stromal maturity, improving the accuracy of the model at a tile, region of interest, and patient level. HistoClean is free and open-source and can be downloaded from the Github repository here: https://github.com/HistoCleanQUB/HistoClean.
The transcription factor Roc1 is a regulator of cellulose degradation in the wood-decaying mushroom Schizophyllum commune
Authors: Marian Ioana M. , Vonk Peter Jan , Valdes Ivan D. , Barry Kerrie , Bostock Benedict , Carver Akiko , Daum Chris , Lerner Harry , Lipzen Anna , Park Hongjae , Schuller Margo B. P. , Tegelaar Martin , Tritt Andrew , Schmutz Jeremy , Grimwood Jane , Lugones Luis G. , Choi In-Geol , Wösten Han A. B. , Grigoriev Igor V. , Ohm Robin A.
Published: June 2021

Wood-decaying fungi of the class Agaricomycetes (phylum Basidiomycota) are saprotrophs that break down lignocellulose and play an important role in the nutrient recycling. They secrete a wide range of extracellular plant cell wall degrading enzymes that break down cellulose, hemicellulose and lignin, the main building blocks of plant biomass. Although the production of these enzymes is regulated mainly at the transcriptional level, no activating regulators have been identified in any wood-decaying fungus in the class Agaricomycetes. We studied the regulation of cellulase expression in the wood-decaying fungus Schizophyllum commune. Comparative genomics and transcriptomics on two wild isolates revealed a Zn2Cys6-type transcription factor gene (roc1) that was highly up-regulated during growth on cellulose, when compared to glucose. It is only conserved in the class Agaricomycetes. A roc1 knockout strain showed an inability to grow on medium with cellulose as sole carbon source, and growth on cellobiose and xylan (other components of wood) was inhibited. Growth on non-wood-related carbon sources was not inhibited. Cellulase activity was reduced in the growth medium of the Δroc1 strain. ChIP-Seq identified 1474 binding sites of the Roc1 transcription factor. Promoters of genes involved in lignocellulose degradation were enriched with these binding sites, especially those of LPMO (lytic polysaccharide monooxygenase) CAZymes, indicating that Roc1 directly regulates these genes. A GC-rich motif was identified as the binding site of Roc1, which was confirmed by a functional promoter analysis. Together, Roc1 is a key regulator of cellulose degradation and the first identified in wood-decaying fungi in the phylum Basidiomycota.
Crystal structure of 1,2-bis(3,5-difluorophenyl)ethane-1,2-dione
Authors: Brown Loren C. , Balaich Gary J.
Published: June 2021

The title compound, C14H6F4O2, crystallizes with half of a molecule per asymmetric unit and exhibits bond lengths and angles typical of α-diketones. A network of C—H...F contacts and π–π stacking interactions is observed within the structure.