bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of internet-based cognitive behavioral therapy on postpartum depression
Authors: Wang Fang , Zhu Hongcheng , Yang Xiaoju , Liao Fang
Published: March 2022

Background:

Postpartum depression is one of the most common complications during the postpartum period. In recent years, internet-based psychological interventions have made significant progress and provided a new psychotherapy model. Internet-based cognitive behavioral therapy (ICBT) for postpartum depression has achieved good results. However, the effectiveness of ICBT for postpartum depression reported by different studies still remains inconsistent. Therefore, a meta-analysis was used to further evaluate the efficacy of ICBT for postpartum depression, aiming to provide evidence to support nonpharmacological intervention strategies in the clinic.

Methods:

The databases of PubMed, Web of Science, Scopus, Cochrane Library, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Data will be searched. The randomized controlled trials of ICBT will be included for postpartum depression published before February 2022. Two independent researchers will independently complete literature selection, risk of bias assessment and data extraction. The disagreements will be discussed with a third party for the final decision. Cochrane Risk of Bias Assessment Tool will be used for literature quality assessment. Data processing will be conducted by RevMan 5.4 software.

Results:

The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusions:

For the question whether ICBT for postpartum depression is efficacy, this study can provide more comprehensive and strong evidence.

Ethics and dissemination:

The ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.

OSF REGISTRATION NUMBER:

DOI 10.17605/OSF.IO/EQJDH.
Effects of Bojungikgi-tang on anorexic patients with atopic dermatitis
Authors: Lee Boram , Park Hyo-Ju , Jung So Young , Kwon O-Jin , Ko Mi Mi , Jeong Hyun Ah , Jung Jeeyoun
Published: March 2022

Background:

Anorexia and atopic dermatitis (AD) are highly prevalent diseases, and the herbal medicine Bojungikgi-tang (BJT) has been frequently used for the treatment of both anorexia and AD. However, no study has simultaneously evaluated the effects of BJT for both anorexia and AD.

Methods:

A prospective, randomized, usual care-controlled, assessor-blinded. parallel, pilot clinical trial has been designed to explore the feasibility, preliminary effectiveness, and safety of BJT for the treatment of anorexic patients with AD. Forty anorexic patients with AD will be randomly assigned (1:1) to BJT or the usual care group. The BJT group will be administered BJT granules twice a day for 8 weeks and followed up for 4 weeks whereas the usual care group will not receive BJT granules. All participants in both groups will be provided with over-the-counter topical corticosteroids as a relief drug. Data will be collected at baseline and at 4, 8, and 12 weeks after randomization. The primary outcome is the score on the anorexia visual analog scale at 8 weeks post-treatment. The secondary outcomes include body weight, body fat percentage, body fat mass, skeletal muscle mass, SCORing of Atopic Dermatitis index, Validated Investigator Global Assessment scale for Atopic Dermatitis, Dermatology Life Quality Index, EuroQoL 5 Dimension 5 Level, deficiency and excess pattern identification questionnaire, total immunoglobulin E, eosinophil count, and frequency and amount of use of topical corticosteroids. Adverse events and laboratory test results will be monitored to assess safety. Fecal samples to check for gut microbiome changes and blood samples to check immune and metabolic markers will be collected before and after taking BJT.

Discussion:

This is the first trial that explores the preliminary effectiveness and safety of BJT for the treatment of anorexic patients with AD. The results of this pilot study will provide the basic evidence for large-scale, confirmatory, multicenter, high-quality clinical trials.

Trial registration:

Clinical Research Information Service, KCT0006784 (registered on November 26, 2021).
Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population
Authors: Mejia Alejandro , Vivian Elaina , Nwogu Christiana , Shah Jimmy , Longoria Raquel , Vo Allison , Shahin Islam , Verma Jonathan , Bageac Alexandru
Published: March 2022

Neuroendocrine tumors (NETs) are rare, but the incidence and prevalence of NETs are increasing in the United States. While surgery is the preferred treatment for NETs, it is not a viable option for metastatic disease. Lutathera (177Lu-DOTATATE) is approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of gastroenteropancreatic (GEP)-NETs in adults. There is limited information on GEP-NET treatment responses to Lutathera.

Our institution launched a peptide receptor radionuclide therapy (PRRT) service line using Lutathera with involvement from a multidisciplinary team and complete collaboration between hospital administration and clinical providers. A prospective registry study was also established in order to collect patient demographics and clinical data regarding the treatment of GEP primary NETs with Lutathera.

Between August 2018 and July 2020, 35 GEP-NET patients were treated with Lutathera, of which 65.71% received 4 complete cycles and 25.71% received 3 cycles; 5.71% and 2.86% received 2 and 1 cycles of PRRT, respectively. Most adverse events during the course of our study were low grade using the common terminology criteria for adverse events system. Of the patients who completed all 4 cycles: 22% showed partial response to Lutathera, 44% showed stable disease, and 13% showed disease progression based on a qualitative assessment of positron emission tomography/computed tomography imaging.

From our experience, Lutathera was well tolerated in patients with GEP-NET. Additional studies are needed to examine long-term clinical and patient-reported outcomes associated with GEP-NET treatment as well as financial considerations for hospitals embarking on a PRRT program.
Future anxiety and coping methods of nursing students during COVID-19 pandemic
Authors: Cetinkaya Senay , Todil Tugba , Kara Mustafa
Published: March 2022

The aim of this research is to examine the methods of nursing students to deal with future anxiety and stress.

It is a cross-sectional survey conducted in Turkey with 291 students in Çukurova University of Faculty of Health Sciences, Kahramanmaraş Sütçü İmam University Health College and Batman University Health College Nursing Department in June 2020. Personal Data Form, Stress Coping Scale, State and Trait Anxiety Scale were sent online to students’ smartphones and/or e-mails as data collection tools and it was collected this way.

The mean age of the participants was 21.09 ± 2.02 (years). 78% of respondents were women. 48.4% of the participants were students of Çukurova University. It was determined that 201 (69.1%) of the participants isolated themselves during the pandemic. It was found that 171 students (58.8%) spent 23 to 24 hours at home, whereas 284 students (97.6%) spent time with their parents/siblings. 47.4% of respondents stated that they had spent the pandemic watching a series/film. 47.1% of respondents had good family relationships. 50.2% of respondents had good relationships with college friends. 74.9% of respondents said they were happy. Women's trait anxiety scale scores were higher than men's (P < .05). Men have higher problem-Oriented coping scores than women (P < .05). Significant differences were found in the Status Anxiety Scale scores and trait anxiety scale scores according to self-isolation status (P < .05). A significant difference was found in terms of state anxiety scale and trait anxiety scale according to happiness status (P < .05). The problem-based coping scores of those who were happy with the Stress Coping Scale were higher than those who were not happy (P < .05). The state anxiety scale of the students was 42.54, and the trait anxiety scale was 45.16.

Nursing students’ status and sustained Anxiety Scale scores were moderate. It is important for individuals to have good family and friends and to be happy in the process of the Corona Virus Disease pandemic.
The impact of physical medicine and rehabilitation consultation on clinical outcomes in the surgical intensive care unit
Authors: Chaiwat Onuma , Sathitkarnmanee Benjaporn , Dajpratham Piyapat , Thanakiattiwibun Chayanan , Jarungjitaree Sunit , Rattanamung Suchera
Published: March 2022

The impact of a physical medicine and rehabilitation (PM&R) consultation on clinical outcomes in critically ill surgical patients remains unclear. The aim of this study is to examine whether the patients who received PM&R consultation will demonstrate better clinical outcomes in terms of the differences in clinical outcomes including muscle mass and strength, intensive care unit (ICU) length of stay (LOS) and functional outcomes between the PM&R consultation and no PM&R consultation and between early PM&R consultation and late PM&R consultation in critically ill surgical patients.

A prospective observational cohort study was undergone in 65-year-old or older patients who were admitted > 24 hours in the surgical intensive care unit (SICU) in a tertiary care hospital. Data collection included patients’ characteristic, muscle mass and muscle strength, and clinical outcomes.

Ninety surgical patients were enrolled and PM&R was consulted in 37 patients (36.7%). There was no significant difference in muscle mass and function between consulted and no consulted groups. PM&R consulted group showed worse in clinical outcomes including functional outcomes at hospital discharge, longer duration of mechanical ventilation, ICU, and hospital LOS as compared with no PM&R consulted group. The median time of rehabilitation consultation was 6 days and there were no significant differences in clinical outcomes between early (≤ 6 days) and late (> 6 days) consultation.

PM&R consultation did not improve muscle mass, functional outcomes at hospital discharge, and ICU LOS in critically ill surgical patients. The key to success might include the PM&R consultation with both intensified physical therapy and early start of mobilization or the rigid mobilization protocol.
Severe dysplasminogenemia due to homozygous PLG Ala620Thr variant in a Korean woman without a history of venous thromboembolism
Authors: Lee Beomki , Kim Suekyeung , Lee Jae Joon , Heo Seon-Hee , Chung Suryeun , Jang Shin Yi , Kim Sun-Hee , Kim Duk-Kyung , Kim Hee-Jin
Published: March 2022

Rationale:

Plasminogen plays an important role in fibrinolysis and is encoded by the PLG gene. The missense variant PLG Ala620Thr is the major cause of dysplasminogenemia in East Asian countries, including Korea. Although dysplasminogenemia was first reported in a Japanese patient with recurrent venous thromboembolism (VTE), subsequent studies have not demonstrated any clear association between the PLG Ala620Thr variant and the risk of VTE. To the best of our knowledge, this is the first report of a homozygous PLG Ala620Thr variant case from Korea.

Patient concerns:

Here, we report a Korean family with PLG Ala620Thr mutation. The proband was a 34-year-old man who presented with multiple thrombotic arterial embolism and cardiac myxoma.

Interventions:

Laboratory workup, including coagulation profile and PLG gene sequencing, was carried out for the affected family.

Diagnosis and Outcome:

The proband carried a heterozygous PLG Ala620Thr variant with decreased plasminogen activity of 65%. His 53-year-old mother, who had no reported history of VTE, was homozygous for the PLG Ala620Thr variant with decreased plasminogen activity of just 25%. Decreased plasminogen activity indicates dysplasminogenemia.

Lessons:

We believe that this clinically silent homozygous case supports the previous findings that isolated PLG Ala620Thr variant does not confer a significant risk of VTE.
Identification of risk factors involved in recurrence after common bile duct stone removal with ERCP
Authors: Akay Tamer , Sari Erdem
Published: March 2022

Recurrent stone detection is common after endoscopic treatment of common bile duct stones (CBDS). This study aimed to identify the risk factors for recurrence of CBDS.

We retrospectively evaluated 14 patients who underwent endoscopic treatment for CBDS. Risk factors for single and multiple recurrent CBDSs were evaluated using logistic regression analysis.

Endoscopic and needle-knife precut sphincterotomy was performed in 506 and 112 patients, respectively. There was 1 recurrence in 85 patients (13.8%), 2 recurrences in 23 patients (3.7%), and 3 recurrences in 9 patients (1.5%). According to the multivariate analyses, being older than 65 years (odds ratio [OR] 1.084, P = .000), concomitant heart disease (OR 2.528, P = .002), concomitant lung disease (OR 1.766, P = .035), a large common bile duct diameter (OR 1.347, P = .000), presence of cholelithiasis (OR 1.752, P = .018), stent (OR 1.794, P = .023), or T-tube placement in the common bile duct (OR 47.385, P = .000), and prolongation of the procedure (OR 1.037, P = .000) increased the risk of recurrence, while having undergone cholecystectomy due to gallstones (OR 1.645, P = .042). The mean stone diameter (P = .059), nitroglycerin use (P = .129), and periampullary diverticulum (P = .891) did not increase the risk of recurrent CBDS.

The probability of multiple recurrences after the first recurrence of CBDS increased with age >65 years, concomitant heart/lung diseases, stent/T-tube placement in the common bile duct, a wide common bile duct (≥10 mm), and cholelithiasis.
Cancer-Related Fatigue: A Pilot Study Evaluating the Effect of Frankincense Essential Oil in Patients With Cancer Receiving Chemotherapy
Authors: Reis Debra , Throne Tisha , Keller Joan , Koffel Christa , Chen Tian , Young-McCaughan Stacey
Published: March 2022

Background

Increasingly, patients with cancer are using essential oils as a complementary therapy to reduce the adverse effects of cancer treatment, such as fatigue. Although essential oils have few adverse effects, little is known about the effectiveness of individual oils for specific symptoms. Frankincense is one such oil that has been identified as a possible supportive therapy for cancer-related fatigue.

Objective

The aim of this study was to determine if frankincense applied to the soles of the feet before, during, and after chemotherapy affects patients’ perceptions of chemotherapy-related fatigue compared with control (carrier oil without frankincense).

Methods

Randomized clinical trial in which participants were blinded to treatment condition. The main outcome variable was fatigue.

Results

Seventy patients undergoing chemotherapy for cancer were randomized to apply frankincense or control oil to their feet twice a day 2 days before receiving chemotherapy, while receiving chemotherapy, and 2 days after chemotherapy. No statistically significant changes in fatigue were found over time or between groups. Baseline fatigue was the only predictor of posttreatment fatigue.

Conclusions

Although no statistically significant changes in fatigue were found over time or between groups, important insights were gained that can inform the design of future research.

Implications for Practice

The use of essential oils as a complementary therapy to reduce adverse effects of cancer treatment is gaining popularity, and nurses may receive questions about the use of essential oils. No evidence to support the use of frankincense in the treatment of fatigue in patients receiving chemotherapy was found in this study.
Managing Complex Medication Regimens
Authors: Harvath Theresa A. , Lindauer Allison , Sexson Kathryn
Published: March 2022

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Foundation. Results of focus groups conducted as part of the AARP Foundation's No Longer Home Alone video project supported evidence that family caregivers aren't being given the information they need to manage the complex care regimens of their family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's medications. Each article explains the principles nurses should consider and reinforce with caregivers and is accompanied by a video for the caregiver to watch. The first video can be accessed at http://links.lww.com/AJN/A74.
Embedding 21st century employability into assessment and feedback practice through a student–staff partnership
Authors: Zainudden Dzachary , Broom Miranda , Nousek-McGregor Anna , Stubbs Fiona , Veitch Nicola
Published: March 2022

In-course assessments are an essential part of any coursework because they represent both a physical output of the skills and knowledge acquired at university, but also have the role of supporting student transitions into prospective careers. Therefore, assessments could be used as a conduit to encourage student awareness of the skills needed for the workplace and verify their attainment of these skills, particularly at foundation levels within a degree. Within a second-year Microbiology and Immunology course, students struggled to engage with standalone timetabled careers-related sessions, yet they showed enthusiasm when employability was embedded into assessments. A staff–student partnership project explored these issues, with the overall aim of understanding how to effectively embed employability skills into assessment and feedback and support students positioning themselves for the future. Through a focus group, this project investigated the reasons for low student engagement with timetabled employability sessions and used student views to develop digital initiatives and 21st-century competencies that could be applied more widely within assessment and feedback practice. These initiatives were then implemented as pre-session self-directed activities, with the objective of helping students to link course feedback with employment skills and future career planning, followed by a newly developed in-class reflective feedback session that allowed students time to consider what skills they have developed and make links with future careers. Project evaluation was conducted using a quantitative survey of the students involved.
Prescription opioid-related alterations to amygdalar and thalamic functional networks in chronic knee pain: A retrospective case control resting-state connectivity study
Authors: Drabek Marianne Marta , Cottam William Joseph , Iwabuchi Sarina Jennifer , Tadjibaev Arman , Mohammadi-Nejad Ali-Reza , Auer Dorothee P
Published: March 2022

Objective

Long-term opioid use is associated with diminished pain relief, hyperalgesia, and addiction which is not well understood. This study aimed to characterise opioid-related brain network alterations in chronic pain, focused on the right amygdala, and left mediodorsal thalamic nuclei that play key roles in affective pain processing, and are particularly rich in mu opioid receptors (MOR).

Subjects

Participants on opioid prescriptions with painful knee osteoarthritis and matched non-opioid using control pain participants.

Methods and design

Seed-based functional connectivity (FC) maps from resting-state fMRI data were compared between groups.

Results

We found right amygdala hyperconnectivity with the posterior default mode network (pDMN) and the dorsomedial prefrontal cortex in opioid users in contrast to anti-correlations in controls. Conversely, opioid users showed predominant hypoconnectivity of the left dorsomedial thalamic seed with the cingulate cortex except for the subgenual part displaying an anti-correlation in opioid users and no association in non-users. Opioid users also showed higher negative affect in exploratory post-hoc tests suggesting a potential contribution of trait anxiety to amygdala-pDMN FC alteration.

Conclusion

Opioid use related hyperconnectivity of the right amygdalar network likely reflects maladaptive mechanisms involving negative affect and network plasticity. Hypoconnectivity of the mediodorsal thalamic nuclei with the anterior and mid cingulate on the other hand may reflect impaired resilience in line with previously reported compensatory MOR upregulation. In conclusion, this study provides new insight into possible brain mechanisms underlying adverse effects of prolonged opioids in chronic pain and offer candidate network targets for novel interventions.
Predicting missed health care visits during the COVID-19 pandemic using machine learning methods: Evidence from 55,500 individuals from 28 European Countries
Authors: Reuter Anna , Smolić Šime , Bärnighausen Till , Sudharsanan Nikkil
Published: March 2022

Background

The COVID-19 pandemic has led many individuals to miss essential care. Machine-learning models that predict which patients are at greatest risk of missing care visits can help health administrators prioritize retentions efforts towards patients with the most need. Such approaches may be especially useful for efficiently targeting interventions for health systems overburdened by the COVID-19 pandemic.

Methods

We compare the performance of four machine learning algorithms to predict missed health care visits based on common patient characteristics available to most health care providers. We use data from 55,500 respondents of the Survey of Health, Ageing and Retirement in Europe (SHARE) COVID-19 survey (June – September 2020) in conjunction with longitudinal data from waves 1-8 (April 2004 – March 2020). We use stepwise selection, group lasso, random forest and neural network algorithms and employ 5-fold cross-validation to test the prediction accuracy, sensitivity, and specificity of the selected models.

Findings

Within our sample, 15.5% of the respondents reported any missed essential health care visit due to the COVID-19 pandemic. All four machine learning methods perform similarly in their predictive power. When classifying all individuals with a predicted probability for missed care above 17% as at risk of a missed visit, they correctly identify between 41% and 53% of the respondents at risk, while correctly identifying between 74% and 64% of the individuals not at risk. We find that the sensitivity and specificity of the models are strongly related to the risk threshold used to classify individuals; thus, the models can be calibrated depending on users’ resource constraints and targeting approach. All models had an area under the curve around 0.62, indicating that they outperform random prediction.

Interpretation

Pandemics such as COVID-19 require rapid and efficient responses to reduce disruptions in health care. Based on characteristics available to health insurance providers, machine learning algorithms can be used to efficiently target efforts to reduce missed essential care.

Funding

Research in this article is a part of the European Union’s H2020 SHARE-COVID19 project (Grant Agreement No. 101015924).
A gain-of-function GRIA2 variant associated with neurodevelopmental delay and seizures: functional characterization and targeted treatment
Authors: Coombs Ian D. , Ziobro Julie , Krotov Volodymyr , Surtees Taryn-Leigh , Cull-Candy Stuart G. , Farrant Mark
Published: March 2022

AMPA-type glutamate receptors (AMPARs) are tetrameric ligand-gated ion channels formed as different combinations of GluA1-4 subunits encoded by the genes GRIA1-4. Various pathogenic variants of these genes have been described in patients with developmental delay, intellectual disability, autistic spectrum disorder and seizures. Here we report a heterozygous de novo pathogenic missense mutation in GRIA2 (c.1928 C>T, p.A643V) identified in a one-year-old male patient with seizures, developmental delay and failure to thrive. Electrophysiological investigation of heterologously expressed receptors showed GluA2 A643V to exhibit greatly slowed deactivation, and a markedly reduced extent of desensitization, compared with wild-type GluA2. When GluA2 A643V was coexpressed with the transmembrane AMPAR regulatory protein (TARP) γ2, or with both GluA1 and γ2 to generate TARPed heteromeric receptors, the slowed deactivation and decreased desensitization persisted. We found that the AMPAR negative allosteric modulator perampanel was able to fully block currents from GluA2 A643V/γ2 receptors, albeit with reduced potency compared with wild-type GluA2/γ2. The introduction of perampanel to the patient’s treatment regimen, alongside a modified Atkins diet, was associated with a marked reduction in seizure number, a resolution of failure to thrive, and clear developmental gains. Our study suggests that AMPAR gain-of-function (GoF) underlies the effect of the GRIA2 variant in our patient, and that perampanel may be beneficial in other patients with GRIA GoF variants.

Author summary

Rapid communication between brain cells is mediated by the excitatory neurotransmitter glutamate. Mutations affecting genes that encode glutamate-gated ion channels can result in neurodevelopmental disorders and seizures. In a young male patient, we identified a mutation in the gene responsible for production of GluA2, a key subunit of AMPA-type glutamate receptors. We showed that receptors containing GluA2 produced by this GRIA2 A643V variant were more sensitive to glutamate and gave rise to unusually prolonged or sustained responses, thus causing ‘gain-of-function’. We found that receptors affected by this mutation could, nonetheless, be inhibited by the AMPA receptor-targeting antiseizure medication, perampanel. Prompted by this finding we introduced perampanel alongside the patient’s ongoing antiseizure medication. This coincided with a decrease in the patient’s seizures and clear developmental gains. Taken together, our findings suggest that a GRIA2 gain-of-function mutation can cause neurological disease, that perampanel can be used to directly counteract the effect of the mutation, and that it may be beneficial in other GRIA gain-of-function patients.
Exploring the experiences of loneliness in adults with mental health problems: a participatory qualitative interview study
Authors: Birken Mary , Chipp Beverley , Shah Prisha , Olive Rachel Rowan , Nyikavaranda Patrick , Hardy Jackie , Chhapia Anjie , Barber Nick , Lee Stephen , Pearce Eiluned , Lloyd-Evans Brynmor , Perkins Rosie , McDaid David , Shafran Roz , Pitman Alexandra , Johnson Sonia
Published: March 2022

Background

Many mental health conditions are associated with loneliness, which is both a potential trigger and an exacerbating factor in mental health conditions. Richer evidence about how people with mental health problems experience loneliness, and about what exacerbates or alleviates it, is needed to underpin research on strategies to help with loneliness in this context.

Methods

Our aim was to explore experiences of loneliness, as well as what contributes to or helps address it, among a diverse sample of adults living with mental health problems in the UK. We recruited purposively via online networks and community organisations. Qualitative semi-structured interviews were conducted with 59 consenting participants by video call or telephone. Researchers with relevant lived experience were involved at all stages, including design, data collection, analysis and writing up of results.

Findings

Analysis led to identification of four overarching themes: 1. What the word “lonely” meant to participants, 2. Contributory factors to ongoing loneliness, 3. Connections between loneliness & mental health, 4. Ways of reducing loneliness. Central aspects of loneliness were lack of meaningful connections with others and lack of a sense of belonging to valued groups and communities. Some drivers of loneliness, such as losses and transitions, were universal, but specific links were made between living with mental health problems and being lonely. These included direct effects of psychiatric symptoms, the need to withdraw to cope with mental health problems, and impacts of stigma and poverty.

Conclusions

The multiplicity of contributors to loneliness that we identified, and of potential strategies for reducing it, suggest that a variety of approaches are relevant to reducing loneliness among people with mental health problems, including peer support and supported self-help, psychological and social interventions, and strategies to facilitate change at community and societal levels. The views and experiences of adults living with mental health problems are a rich source for understanding why loneliness is a frequent experience in this context and what may address it. Co-produced approaches to developing and testing interventions have potential to draw on this experiential knowledge in formulating effective approaches to loneliness.
Personalised structural connectomics for moderate-to-severe traumatic brain injury
Authors: Imms Phoebe , Clemente Adam , Deutscher Evelyn , Radwan Ahmed M. , Akhlaghi Hamed , Beech Paul , Wilson Peter H , Irimia Andrei , Poudel Govinda , Domínguez D Juan F , Caeyenberghs Karen
Published: March 2022

Graph theoretical analysis of the structural connectome has been employed successfully to characterise brain network alterations in patients with traumatic brain injury (TBI). However, heterogeneity in neuropathology is a well-known issue in the TBI population, such that group comparisons of patients against controls are confounded by within-group variability. Recently, novel single-subject profiling approaches have been developed to capture inter-patient heterogeneity. We present a personalised connectomics approach that examines structural brain alterations in six chronic patients with moderate-to-severe TBI who underwent anatomical and diffusion magnetic resonance imaging (MRI). We generated individualised profiles of lesion characteristics and network measures (including personalised graph metric ‘GraphMe’ plots, and nodal and edge-based brain network alterations) and compared them against healthy reference cases (N=12) to assess brain damage qualitatively and quantitatively at the individual level. Our findings revealed clinically significant alterations of brain networks with high variability between patients. Our profiling can be used by clinicians to formulate a neuroscience-guided integrative rehabilitation program for TBI patients, and for designing personalised rehabilitation protocols based on their unique lesion load and connectome.
Systematic hyper-variation and evolution at a lipopolysaccharide locus in the population of Xanthomonas species that infect rice and sugarcane
Authors: Singh Anu , Bansal Kanika , Kumar Sanjeet , Patil Prabhu B.
Published: March 2022

Advent of high throughput sequencing and population genomics is enabling researchers to investigate selection pressure at hyper-variable genomic loci encoding pathogen-associated molecular patter (PAMP) molecules like lipopolysaccharide (LPS) in an unprecedented manner. Xanthomonas is a model group of phytopathogenic bacteria that infects host in tissue-specific manner. Our in-depth investigation revealed that the successful emergence of lineages infecting major cereals and grasses like rice, sugarcane, and wheat was mediated by acquisition and later replacement of an ancestral type (BXO8) of LPS cassette by distinct one. In the population of the rice xylem pathogen, X. oryzae pv. oryzae (Xoo), the BXO8 is replaced by a distinct BXO1 type of cassette. Alternatively, in diverse Xanthomonas species that infect sugarcane, the BXO8 ancestral cassette has been replaced by yet another kind of Xvv type of LPS cassette, suggesting convergent evolution at an LPS locus mediated by horizontal gene transfer (HGT) events. Aside from xylem, two closely related lineages of X. oryzae that infect parenchyma tissue of rice and Leersia hexandra grass have acquired an LPS cassette from Xanthomonas pathogens that infect citrus, walnut, and strawberry parenchyma, indicating yet another instance of parallel evolution facilitated by HGT. Our targeted and mega-population-based genome dynamic studies revealed potential role of acquisition of specific types of LPS cassettes in the emergence and evolution of tissue specificity in Xanthomonas. Additional cellular, molecular, genetic, and plant studies will help us figure out how a distinct type of LPS help Xanthomonas pathovars and lineages adapt to parenchyma and xylem tissues.
Rpadrino: an R package to access and use PADRINO, an open access database of Integral Projection Models
Authors: Levin Sam C. , Evers Sanne , Potter Tomos , Guerrero Mayra Peña , Childs Dylan Z. , Compagnoni Aldo , Knight Tiffany M. , Salguero-Gómez Roberto
Published: March 2022

Discrete time structured population projection models are an important tool for studying population dynamics. Within this field, Integral Projection Models (IPMs) have become a popular method for studying populations structured by continuously distributed traits(e.g.height, weight). Databases of discrete time, discrete state structured population models, for example DATLife (life tables) and COMPADRE & COMADRE (matrix population models), have made quantitative syntheses straightforward to implement. These efforts allow researchers to address questions in both basic and applied ecology and evolutionary biology. There are now over 300 peer-reviewed publications containing IPMs. We describe a novel framework to quickly reconstruct these models for subsequent analyses usingRpadrino Rpackage, which serves as an interface to PADRINO, a new database of structured population models.

We introduce an R package,Rpadrino,which enables users to download, subset, reconstruct, and extend published IPMs.Rpadrinomakes use of recently created software,ipmr,to provide an engine to reconstruct a wide array of IPMs from their symbolic representations and conduct subsequent analyses.Rpadrinoandipmrare extensively documented to help users learn their usage.

Rpadrinocurrently enables users to reconstruct 280 IPMs from 40 publications that describe the demography of 14 animal and 26 plant species. All of these IPMs are tested to ensure they reproduce published estimates.Rpadrinoprovides an interface to augment PADRINO with external data and modify parameter values, creating a platform to extend models beyond their original purpose while retaining full reproducibility.

PADRINO andRpadrinoprovide a toolbox for asking new questions and conducting syntheses with peer-reviewed published IPMs.Rpadrinoprovides a user-friendly interface so researchers do not need to worry about the database structure or syntax, and can focus on their research questions and analyses. Additionally,Rpadrinois thoroughly documented, and provides numerous examples of how to perform analyses which are not included in the package’s functionality.
AMP-activated protein kinase (AMPK) is required for recovery from metabolic stress induced by ultrasound microbubble treatment
Authors: Lo Louis , Uchenunu Oro , Botelho Roberto J. , Antonescu Costin N. , Karshafian Raffi
Published: March 2022

Ultrasound and microbubbles (USMB) is a promising strategy for cancer therapy. USMB can induce a variety of effects on cells including transient formation of plasma membrane pores (sonoporation) and enhanced endocytosis, which enhance drug delivery, and can also lead to enhanced cell death. However, the outcomes of USMB on cell physiology are heterogeneous, in that USMB elicits cell death in a proportion of cells while exerting minimal effects on others. This suggests that mechanisms of adaptation following USMB allow some cells to survive and/or proliferate. The molecular mechanisms of adaptation to USMB-induced stress remain poorly understood, thus potentially hindering broad therapeutic applications of USMB. Herein, we used several triple negative breast cancer cells to study the effect of USMB-induced metabolite stress and the role of AMPK as a response to this stress. We found that USMB alters steady-state levels of amino acids, glycolytic intermediates, and citric acid cycle intermediates. USMB treatment acutely reduces ATP levels and stimulates AMP-activated protein kinase (AMPK) phosphorylation and activation. Further, AMPK is required to restore ATP levels in cells that survived the initial insult and support cell proliferation post-USMB treatment. These results suggest that AMPK and metabolic perturbations are likely determinants of the anti-neoplastic efficacy of USMB treatment.
Evaluation of N6-adenine DNA-immunoprecipitation-based genomic profiling in eukaryotes
Authors: Debo Brian M. , Mallory Ben , Stergachis Andrew B.
Published: March 2022

The detection of low-abundance DNA N6-methyladenine (DNA-m6A) remains challenging, limiting our understanding of this novel base in eukaryotes. To address this, we introduce an approach for systematically validating the selectivity and sensitivity of antibody-based DNA-m6A methods, revealing most commercial antibodies as poorly selective towards DNA-m6A. Finally, using a validated highly selective anti-DNA-m6A antibody we expose distinct patterns of DNA-m6A in C. reinhardtii, A. thaliana, and D. melanogaster.
Predicting sex, age, general cognition and mental health with machine learning on brain structural connectomes
Authors: Yeung Hon Wah , Stolicyn Aleks , Buchanan Colin R. , Tucker-Drob Elliot M. , Bastin Mark E. , Luz Saturnino , McIntosh Andrew M. , Whalley Heather C. , Cox Simon R. , Smith Keith
Published: March 2022

There is increasing expectation that advanced, computationally expensive machine learning techniques, when applied to large population-wide neuroimaging datasets, will help to uncover key differences in the human brain in health and disease. We take a comprehensive approach to explore how multiple aspects of brain structural connectivity can predict sex, age, general cognitive function and general psychopathology, testing different machine learning algorithms from deep learning model (BrainNetCNN) to classical machine learning methods. We modelledN= 8, 183 structural connectomes from UK Biobank using six different structural network weightings obtained from diffusion MRI. Streamline count generally provided highest prediction accuracies in all prediction tasks. Deep learning did not improve on prediction accuracies from simpler linear models. Further, high correlations between gradient attribution coefficients from deep learning and model coefficients from linear models suggested the models ranked the importance of features in similar ways, which indirectly suggested the similarity in models’ strategies for making predictive decision to some extent. This highlights that model complexity is unlikely to improve detection of associations between structural connectomes and complex phenotypes with the current sample size.
Optimization of dynamic soaring in a flap-gliding seabird and its impacts on large-scale distribution at sea
Authors: Kempton James A. , Wynn Joe , Bond Sarah , Evry James , Fayet Annette L. , Gillies Natasha , Guilford Tim , Kavelaars Marwa , Juarez-Martinez Ignacio , Padget Oliver , Rutz Christian , Shoji Akiko , Syposz Martyna , Taylor Graham K.
Published: March 2022

Dynamic soaring harvests energy from a spatiotemporal wind gradient, allowing albatrosses to glide over vast distances. However, its use is challenging to demonstrate empirically, and has yet to be confirmed in other seabirds. Here we investigate how flap-gliding Manx Shearwaters optimise their flight for dynamic soaring. We do so by deriving a new metric, the horizontal wind effectiveness, that quantifies how effectively flight harvests energy from a shear layer. We evaluate this metric empirically for fine-scale trajectories reconstructed from bird-borne video data using a simplified flight dynamics model. We find that the birds’ undulations are phased with their horizontal turning to optimise energy harvesting. We also assess the opportunity for energy harvesting in long-range, GPS-logged foraging trajectories, and find that Manx Shearwaters optimise their flight to increase the opportunity for dynamic soaring during favourable wind conditions. Our results show how small-scale dynamic soaring impacts large-scale Manx Shearwater distribution at sea.

Teaser

Flap-gliding shearwaters harvest wind energy by fine-scale trajectory optimization and this impacts their large-scale distribution at sea.
Intrinsic Protein Disorder, Conditional Folding and AlphaFold2
Authors: Piovesan Damiano , Monzon Alexander Miguel , Tosatto Silvio C.E.
Published: March 2022

Intrinsically disordered regions (IDRs) defying the traditional protein structure-function paradigm have been difficult to analyze. AlphaFold’s recent breakthrough in predicting protein structures accurately offers a fresh perspective on IDR prediction as assessed on the CAID dataset. Surprisingly, AlphaFold is highly competitive for predicting both IDRs and conditionally folded regions, demonstrating the plasticity of the disorder to structure continuum.
One-pot synthesis of prenylated proteins utilizing E. coli cell-free expression
Authors: Kai Lei , Sonal  , Heermann Tamara , Schwille Petra
Published: March 2022

Bottom-up synthetic biology is a powerful tool for uncovering the mechanisms underlying vital biological processes, such as signaling and cell polarization. The core principle of reconstituting cellular functions in their minimal forms can be achieved through modular protein design. However, assembling multiple purified proteins into a functional and synchronized system remains a technical challenge. The fact that many regulatory proteins show direct or indirect membrane interactions further exacerbates the complications. Here, we introduce the Cell-Free prenylated Protein Synthesis (CFpPS) system which enables the production of prenylated proteins in a single reaction mix, through reconstituted prenylation machinery. Not only does the CFpPS system offer a fast and reliable method for producing solubilized prenylated proteins, but it can also produce the protein of interest directly in the vicinity of biomimetic membranes, thus enabling microscopy-based functional assessment. As proof of principle, we demonstrate synthesis and solubilization of various important signaling proteins from the Ras superfamily, as well as membrane binding and extraction of the key polarity regulator Cdc42. Furthermore, our method can be used to confer membrane affinity to any protein, simply by adding a 4-peptide motif to the C-terminus of the protein. In sum, the CFpPS system offers a versatile and effective platform for designing peripheral membrane proteins for synthetic biology applications.
The molecular chaperone Cysteine String Protein is required to stabilize trans-SNARE complexes during human sperm acrosomal exocytosis
Authors: Montero Karina Flores , Berberián María Victoria , Mayorga Luis Segundo , Tomes Claudia Nora , Ruete María Celeste
Published: March 2022

Membrane fusion in sperm cells is crucial for acrosomal exocytosis and must be preserved to assure fertilizing capacity. Evolutionarily conserved protein machinery regulates acrosomal exocytosis. Molecular chaperones play a vital role in spermatogenesis and post-testicular maturation. Cysteine String Protein (CSP) is a member of the Hsp40 co-chaperones, and for more than 20 years, most research published focused on CSP’s role in synapsis. However, the participation of molecular chaperones in acrosomal exocytosis is poorly understood. Using western blot and indirect immunofluorescence, we showed that CSP is present in human sperm, is predominantly bound to membranes, and is palmitoylated. Moreover, using electron microscopy and functional assays, we reported that sequestration of CSP avoided the assembly of trans-complexes and inhibited exocytosis. In summary, our data demonstrated that CSP is necessary and mediates the trans-SNARE complex assembly between the outer acrosomal and plasma membranes, thereby regulating human sperm acrosomal exocytosis. Understanding CSP’s role is critical in identifying new biomarkers and generating new rational-based approaches to treating male infertility.

Summary statement

Cysteine String Protein is necessary and mediates the trans-SNARE complex assembly between the outer acrosomal and plasma membranes, thereby regulating human sperm acrosomal exocytosis.
Helminth parasites decrease survival probability in young red deer
Authors: Acerini Claudia I. , Morris Sean , Morris Alison , Kenyon Fiona , McBean David , Pemberton Josephine M. , Albery Gregory F.
Published: March 2022

Helminths are common parasites of wild ungulates that can have substantial costs for growth, mortality, and reproduction. While these costs are relatively well documented for mature animals, knowledge of helminths’ impacts on juveniles is more limited. Identifying these effects is important because young individuals are often heavily infected, and juvenile mortality is an important process regulating wild populations. Here, we investigated associations between helminth infection and overwinter survival in juvenile wild red deer (Cervus elaphus) on the Isle of Rum, Scotland. We collected faecal samples non-invasively from known individuals and used them to count propagules of three helminth taxa (strongyle nematodes,Fasciola hepatica, andElaphostrongylus cervi). Using generalised linear models, we investigated associations between parasite counts and overwinter survival for calves and yearlings. Strongyles were associated with reduced survival in both age class, andF. hepaticawas associated with reduced survival in yearlings, whileE. cerviinfection showed no association with survival in either age class. This study provides observational evidence for fitness costs of helminth infection in juveniles of a wild mammal, and suggests that these parasites could play a role in regulating population dynamics.
Employee treatment and discontinued operations
Authors: Leonard Lori , Sun Li
Published: March 2022

Purpose

The authors investigate the relation between employee treatment and the likelihood of discontinuing business operations.

Design/methodology/approach

The authors use regression analysis to investigate the relation between employee treatment and the likelihood of discontinuing business operations.

Findings

The authors find a significant negative relation between employee treatment and the likelihood of discontinuing business operations, suggesting that firms with better employee treatment are less likely to discontinue operations.

Originality/value

This study contributes to two distinctive steams of research: discontinued operations in accounting literature and employee welfare in human resources management literature.