bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating prolonged social withdrawal behaviour as a risk factor for self-harm and suicidal behaviours
Authors: Zhu Shimin , Lee Paul H. , Wong Paul W. C.
Published: April 2021

Background

Self-harm and suicidal behaviour are recognised as public health concerns. Prolonged social withdrawal behaviour, orhikikomori, is reported as a risk factor for suicidal behaviour.

Aims

To examine the occurrence and additional risk of prolonged social withdrawal behaviour on self-harm and suicidal behaviour among Chinese university students.

Method

A cross-sectional online survey was conducted with three universities in southern China. A two-stage random sampling was adopted for recruitment, with students in different years of study, in different departments of each participating university. Hierarchical logistic regression analyses were conducted to investigate the sociodemographic and psychological correlates of self-harm and suicidal behaviours among male and female participants withhikikomoristatus.

Results

Of the students who completed the online survey, 1735 (72.23%) were included in the analysis; 11.5% (n= 200) reported self-harm behaviour and 11.8% (n= 204) reported suicidal behaviours in the past 12 months. Men showed a higher prevalence rate of self-harm than women (14.7%v.10.8%,P= 0.048), but a similar rate of suicidal behaviours (11.9%v.11.3%,P= 0.78). The overall prevalence rate of social withdrawal behaviour was 3.2% (7.0% for men and 2.3% for women,P< 0.001). Prolonged social withdrawal behaviour status was significantly associated with self-harm (odds ratio 2.00, 95% CI 1.22–3.29) and suicidal behaviour (odds ratio 2.35, 95% CI 1.45–3.81). However, the associations became statistically insignificant after adjustment for psychological factors in the final models in the logistic regression analyses.

Conclusions

Prolonged social withdrawal behaviour appears to be associated with self-harm and suicidal behaviour, but psychological factors have stronger links with suicidality.
Associations between hemispheric asymmetry and schizophrenia-related risk genes in people with schizophrenia and people at a genetic high risk of schizophrenia
Authors: Zhu Yue , Wang Shuai , Gong Xiaohong , Edmiston Elliot K. , Zhong Suyu , Li Chao , Zhao Pengfei , Wei Shengnan , Jiang Xiaowei , Qin Yue , Kang Jujiao , Wang Yi , Sun Qikun , Gong Gaolang , Wang Fei , Tang Yanqing
Published: April 2021

Background

Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.

Aims

To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.

Method

A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored.

Results

There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.

Conclusions

The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.
Differences in Toxicity and Outcomes in Clinical Trial Participants From Minority Populations
Authors: Labriola Matthew , George Daniel J.
Published: April 2021

Black men have a higher prevalence of and mortality rate from prostate cancer compared with White men and have been shown to present with more aggressive and later-stage disease. How prostate cancer treatment affects these racial disparities is still unclear. Several studies have shown that Black men who receive treatment have a more pronounced decrease in prostate cancer–specific death; however, there remains a large disparity in all-cause mortality. This disparity may be in part related to a higher risk of death resulting from comorbidities, given the higher rates of cardiovascular disease and diabetes in Black men, both of which are complicated by the use of androgen-deprivation therapy. To further understand these disparities, it is important that we analyze the racial differences in adverse event rates and severity. Increasing the percentage of Black men in clinical trials will improve the understanding of the biologic drivers of racial disparities in prostate cancer. To evaluate the potential differences in adverse event reporting and demonstrate the feasibility of enrolling equal numbers of Black and White men in trials, we performed a prospective, multicenter study of abiraterone plus prednisone with androgen-deprivation therapy in men with metastatic castration-resistant prostate cancer, stratified by race. Racial differences in prostate-specific antigen kinetics and toxicity profile were demonstrated. Higher rates and severity of adverse events related to adrenal hormone suppression, including hypertension, hypokalemia, and hypomagnesemia, were seen in the Black cohort, not previously reported. Increased enrollment of Black men in prostate cancer clinical trials is imperative to further understand the impact of race on clinical outcomes and treatment tolerability.
Personalizing Medicine With Germline and Somatic Sequencing in Advanced Pancreatic Cancer: Current Treatments and Novel Opportunities
Authors: Lee Michael S. , Pant Shubham
Published: April 2021

Performing germline and somatic sequencing in locally advanced and metastatic pancreatic cancer can identify potentially targetable genomic aberrations that impact current standard treatment options or eligibility for biomarker-targeted clinical trials. Testing for deleterious germline mutations in BRCA1/2 impacts patient selection for platinum-based chemotherapy regimens and selection of patients who are candidates to receive maintenance therapy with olaparib. Additional germline mutations also similarly introduce potential vulnerabilities to the cancers that arise and may be targeted by clinical trials. Somatic mutation testing also provides opportunities for optimal selection of patients for biomarker-driven clinical trials. Although KRAS mutations are found in 90% to 93% of pancreatic cancers, there are increasing opportunities for therapies against particular mutant KRAS isoforms, especially with the advent of KRAS G12C–specific small molecule inhibitors, and KRAS targeting trials will increasingly require identification of the specific KRAS mutation present. There are also a range of tumor site–agnostic molecular features, such as microsatellite instability and NTRK fusions that, although rarely found in pancreatic cancers, impact selection of patients who have the potential for dramatic benefit with immune checkpoint inhibitors such as pembrolizumab or TRK inhibitors such as larotrectinib or entrectinib, respectively, and thus motivate broader somatic mutation and fusion testing for patients with locally advanced and metastatic pancreatic cancers. Multiple other rare actionable aberrations, particularly gene fusions in the 8% to 10% of KRAS wild-type pancreatic cancers, are also known, and enrollment in basket trials for these rare patient cohorts is highly encouraged.
Screen, Notify, See, and Treat: Initial Results of Cervical Cancer Screening and Treatment in Rwanda
Authors: Muhimpundu Marie-Aimee , Ngabo Fidele , Sayinzoga Felix , Balinda Jean Paul , Rusine John , Harward Sardis , Eagan Arielle , Krivacsy Sara , Bayingana Alice , Uwimbabazi Jean Claude , Makuza Jean Damascene , Ngirabega Jean de Dieu , Binagwaho Agnes
Published: April 2021

PURPOSE

To describe the first year results of Rwanda's Screen, Notify, See, and Treat cervical cancer screening program, including challenges encountered and revisions made to improve service delivery.

METHODS

Through public radio broadcasts, meetings of local leaders, church networks, and local women's groups, public awareness of cervical cancer screening opportunities was increased and community health workers were enlisted to recruit and inform eligible women of the locations and dates on which services would be available. Screening was performed using human papillomavirus (HPV) DNA testing technology, followed by visual inspection with acetic acid (VIA), and cryotherapy, biopsy, and surgical treatment for those who tested HPV-positive. These services were provided by five district hospitals and 15 health centers to HIV-negative women of age 35-45 and HIV-positive women of age 30-50. Service utilization data were collected from the program's initiation in September 2013 to October 2014.

RESULTS

Of 7,520 cervical samples tested, 874 (11.6%) screened HPV-positive, leading 780 (89%) patients to undergo VIA. Cervical lesions were found in 204 patients (26.2%) during VIA; of these, 151 were treated with cryoablation and 15 were referred for biopsies. Eight patients underwent complete hysterectomy to treat advanced cervical cancer. Challenges to service delivery included recruitment of eligible patients, patient loss to follow-up, maintaining HIV status confidentiality, and efficient use of consumable resources.

CONCLUSION

Providing cervical cancer screening services through public health facilities is a feasible and valuable component of comprehensive women's health care in resource-limited settings. Special caution is warranted in ensuring proper adherence to follow-up and maintaining patient confidentiality.
Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation
Authors: Olson Amanda , Lin Ruitao , Marin David , Rafei Hind , Bdiwi Mustafa H. , Thall Peter F. , Basar Rafet , Abudayyeh Ala , Banerjee Pinaki , Aung Fleur M. , Kaur Indresh , Abueg Glorette , Rao Sheetal , Chemaly Roy , Mulanovich Victor , Al-Atrash Gheath , Alousi Amin M. , Andersson Borje S. , Anderlini Paolo , Bashir Qaiser , Castro Karla M. , Daher May , Galvan Isabel M. , Hosing Chitra , Im Jin S. , Jones Roy B. , Kebriaei Partow , Khouri Issa , Mehta Rohtesh , Molldrem Jeffrey , Nieto Yago , Oran Betul , Popat Uday , Qazilbash Muzaffar , Rondon Gabriela , Saini Neeraj , Spencer Bryan , Srour Samer , Washington Dominique , Barnett Melissa , Champlin Richard E. , Shpall Elizabeth J. , Rezvani Katayoun
Published: April 2021

PURPOSE

BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option.

METHODS

We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698 ) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed.

RESULTS

Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.

CONCLUSION

Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study
Authors: Hughes Christopher G. , Hayhurst Christina J. , Pandharipande Pratik P. , Shotwell Matthew S. , Feng Xiaoke , Wilson Jo Ellen , Brummel Nathan E. , Girard Timothy D. , Jackson James C. , Ely E. Wesley , Patel Mayur B.
Published: April 2021

BACKGROUND:

The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year.

METHODS:

We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium.

RESULTS:

Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2–7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2–7) days and 1 (1–2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year.

CONCLUSIONS:

Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.
Preparing Anesthesiology Residents for Operating Room Communication Challenges: A New Approach for Conflict Resolution Training
Authors: Birnbach David J. , Rosen Lisa F. , Fitzpatrick Maureen , Shekhter Ilya , Arheart Kristopher L.
Published: April 2021

BACKGROUND:

The hierarchical culture in high-stake areas such as operating rooms (ORs) may create volatile communication challenges. This unfunded exploratory study sought to establish whether a conflict resolution course was effective in preparing anesthesiology residents to handle and deescalate disagreements that may arise in the clinical environment, especially when challenging a surgeon.

METHODS:

Thirty-seven anesthesiology residents were assessed for ability to deescalate conflict. Nineteen had completed a conflict resolution course, and 18 had not. The 2-hour course used 10 videotaped vignettes that showed attending anesthesiologists, patients, and surgeons challenging residents in a potentially confrontational situation. Guided review of the videos and discussions was focused on how the resident could optimally engage in conflict resolution. To determine efficacy of the conflict resolution course, we used simulation-based testing. The setting was a simulated OR with loud music playing (75–80 dB) under the control of the surgeon. The music was used as a tool to create a potential, realistic confrontation with the surgeon to test conflict resolution skills. The initial evaluation of the resident was whether they ignored the music, asked for the surgeon to turn it off, or attempted to turn it off themselves. The second evaluation was whether the resident attempted to deescalate (eg, calmly negotiate for the music to be turned off or down) when the surgeon was scripted to adamantly refuse. Two trained observers evaluated residents’ responses to the surgeon’s refusal.

RESULTS:

Of the residents who experienced the confrontational situation and had not yet taken the conflict resolution course, 1 of 5 (20.0%; 95% CI, 0.5–71.6) were judged to have deescalated the situation. In comparison, of those who had taken the course, 14 of 15 (93.3%; 95% CI, 68.1–99.8) were judged to have deescalated the situation (P = .002). Only 2 of 19 (10.5%; 95% CI, 1.3–33.1) of those who completed the course ignored the music on entering the OR versus 10 of 18 (55.6%; 95% CI, 30.8–78.5) who did not complete the course (P = .004).

CONCLUSIONS:

This study suggests that a conflict resolution course may improve the ability of anesthesiology residents to defuse clinical conflicts. It also demonstrated the effectiveness of a novel, simulation-based assessment of communication skills used to defuse OR confrontation.
The Evaluation of a Noninvasive Respiratory Volume Monitor in Mechanically Ventilated Neonates and Infants
Authors: Atkinson Douglas B. , Sens Brooke A. , Bernier Rachel S. , Gomez-Morad Andrea D. , Imsirovic Jasmin , Nasr Viviane G.
Published: April 2021

BACKGROUND:

The respiratory volume monitor (RVM) (ExSpiron, Respiratory Motion Inc, Watertown, MA) uses thoracic impedance technology to noninvasively and continuously measure tidal volume (TV), respiratory rate (RR), and minute ventilation (MV). We aimed to validate the accuracy of the RVM to assess ventilation in neonates and infants by comparing it to spirometry.

METHODS:

We used the RVM and Respironics NM3 spirometer (Respironics NM3 Respiratory Profile Monitor, Philips Healthcare, Amsterdam, the Netherlands) to record simultaneous and continuous measurements of MV, TV, and RR. The RVM measurements, with and without external calibration, were compared to the Respironics NM3 spirometer using Bland-Altman analysis. The relative errors (Bland-Altman) between RVM and Respironics NM3 were calculated and used to compute individual patient bias, precision, and accuracy as the mean error, the standard deviation (SD) of the error, and the root mean square error. Bland-Altman limits of agreement (LoA) were computed, and equivalence tests were performed.

RESULTS:

Forty patients were studied to compare the RVM and Respironics NM3 measurements. The mean difference (ie, bias) for MV was 1.8% with 95% LoA, defined as mean ± 1.96 SD, in the range of −12.1% to 15.7%. Similarly, the mean difference (ie, bias) for TV and RR was 1.2% (95% LoA, −11.0% to 13.5%) and 0.6% (95% LoA, −3.7% to 5.0%), respectively. The mean measurement precision of the RVM relative to the Respironics NM3 for MV, TV, and RR was 10.8%, 8.9%, and 8.4%, respectively. The mean measurement accuracy for MV, TV, and RR across patients was 11.0%, 9.7%, and 7.1%, respectively.

CONCLUSIONS:

The data demonstrate that the RVM measures TV and MV in this cohort with an average relative error of 11% when using patient calibration and 16.9% without patient calibration. The average relative error of RR was 7.1%. The RVM provides accurate measurement of RR, TV, and MV in mechanically ventilated neonates and infants.
Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury
Authors: Müller-Wirtz Lukas Martin , Kiefer Daniel , Maurer Felix , Floss Maximilian Alexander , Doneit Jonas , Hüppe Tobias , Shopova Theodora , Wolf Beate , Sessler Daniel I. , Volk Thomas , Kreuer Sascha , Fink Tobias
Published: April 2021

BACKGROUND:

Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats.

METHODS:

A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL·kg−1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL·kg−1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL·kg−1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg−1 before returning to a tidal volume of 6 mL·kg−1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column–ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue.

RESULTS:

Exhaled pentanal concentrations increased by only 0.5 ppb·h−1 (95% confidence interval [CI], 0.3–0.6) when rats were ventilated at 6 mL·kg−1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb·h−1 (95% CI, 2.3–3.8) at tidal volumes of 20 mL·kg−1. Exhaled pentanal increased at average rates between 1.0 ppb·h−1 (95% CI, 0.3–1.7) and 2.5 ppb·h−1 (95% CI, 1.4–3.6) after the onset of 16 mL·kg−1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9–3.2), corresponding to a 38% (IQR, 31–43) reduction when tidal volume returned to 6 mL·kg−1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue.

CONCLUSIONS:

Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats.
Reckoning with Slavery
Authors: Morgan Jennifer L.
Published: April 2021

In Reckoning with Slavery Jennifer L. Morgan draws on the lived experiences of enslaved African women in the sixteenth and seventeenth centuries to reveal the contours of early modern notions of trade, race, and commodification in the Black Atlantic. From capture to transport to sale to childbirth, these women were demographically counted as commodities during the Middle Passage, vulnerable to rape, separated from their kin at slave markets, and subject to laws that enslaved their children upon birth. In this way, they were central to the binding of reproductive labor with kinship, racial hierarchy, and the economics of slavery. Throughout this groundbreaking study, Morgan demonstrates that the development of Western notions of value and race occurred simultaneously. In so doing, she illustrates how racial capitalism denied the enslaved their kinship and affective ties while simultaneously relying on kinship to reproduce and enforce slavery through enslaved female bodies.
Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease
Authors: Smith Blake R. C. , Nyström Alexander , Nowell Cameron J. , Hausser Ingrid , Gretzmeier Christine , Robertson Susan J. , Varigos George A. , Has Cristina , Kern Johannes S. , Pang Ken C.
Published: April 2021

Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa.

This article has an associated First Person interview with the first author of the paper.
Ccdc103 promotes myeloid cell proliferation and migration independent of motile cilia
Authors: Falkenberg Lauren G. , Beckman Sarah A. , Ravisankar Padmapriyadarshini , Dohn Tracy E. , Waxman Joshua S.
Published: April 2021

The pathology of primary ciliary dyskinesia (PCD) is predominantly attributed to impairment of motile cilia. However, PCD patients also have perplexing functional defects in myeloid cells, which lack motile cilia. Here, we show that coiled-coil domain-containing protein 103 (CCDC103), one of the genes that, when mutated, is known to cause PCD, is required for the proliferation and directed migration of myeloid cells. CCDC103 is expressed in human myeloid cells, where it colocalizes with cytoplasmic microtubules. Zebrafish ccdc103/schmalhans (smh) mutants have macrophages and neutrophils with reduced proliferation, abnormally rounded cell morphology and an inability to migrate efficiently to the site of sterile wounds, all of which are consistent with a loss of cytoplasmic microtubule stability. Furthermore, we demonstrate that direct interactions between CCDC103 and sperm associated antigen 6 (SPAG6), which also promotes microtubule stability, are abrogated by CCDC103 mutations from PCD patients, and that spag6 zebrafish mutants recapitulate the myeloid defects observed in smh mutants. In summary, we have illuminated a mechanism, independent of motile cilia, to explain functional defects in myeloid cells from PCD patients.

This article has an associated First Person interview with the first author of the paper.
Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells
Authors: Nodari Alice , Scambi Ilaria , Peroni Daniele , Calabria Elisa , Benati Donatella , Mannucci Silvia , Manfredi Marcello , Frontini Andrea , Visonà Silvia , Bozzato Andrea , Sbarbati Andrea , Schena Federico , Marengo Emilio , Krampera Mauro , Galiè Mirco
Published: April 2021

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched-chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the ‘sterile’ activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.
Acoustically eavesdropping bat predators take longer to capture katydid prey signalling in aggregation
Authors: Prakash Harish , Greif Stefan , Yovel Yossi , Balakrishnan Rohini
Published: April 2021

Prey that are signalling in aggregation become more conspicuous with increasing numbers and tend to attract more predators. Such grouping may, however, benefit prey by lowering the risk of being captured because of the predator's difficulty in targeting individuals. Previous studies have investigated anti-predatory benefits of prey aggregation using visual predators, but it is unclear whether such benefits are gained in an auditory context. We investigated whether katydids of the genus Mecopoda gain protection from their acoustically eavesdropping bat predator Megaderma spasma when calling in aggregation. In a choice experiment, bats approached calls of prey aggregations more often than those of prey calling alone, indicating that prey calling in aggregation are at higher risk. In prey capture tasks, however, the average time taken and the number of flight passes made by bats before capturing a katydid were significantly higher for prey calling in aggregation than when calling alone, indicating that prey face lower predation risk when calling in aggregation. Another common anti-predatory strategy, calling from within vegetation, increased the time taken by bats to capture katydids calling alone but did not increase the time taken to capture prey calling from aggregations. The increased time taken to capture prey calling in aggregation compared with solitary calling prey offers an escape opportunity, thus providing prey that signal acoustically in aggregations with anti-predatory benefits. For bats, greater detectability of calling prey aggregations is offset by lower foraging efficiency, and this trade-off may shape predator foraging strategies in natural environments.
Scavenging of reactive oxygen species mimics the anoxic response in goldfish pyramidal neurons
Authors: Pillai Varshinie , Buck Leslie , Lari Ebrahim
Published: April 2021

Goldfish are one of a few species able to avoid cellular damage during month-long periods in severely hypoxic environments. By suppressing action potentials in excitatory glutamatergic neurons, the goldfish brain decreases its overall energy expenditure. Coincident with reductions in O2 availability is a natural decrease in cellular reactive oxygen species (ROS) generation, which has been proposed to function as part of a low-oxygen signal transduction pathway. Using live-tissue fluorescence microscopy, we found that ROS production decreased by 10% with the onset of anoxia in goldfish telencephalic brain slices. Employing whole-cell patch-clamp recording, we found that, similar to severe hypoxia, the ROS scavengers N-acetyl cysteine (NAC) and MitoTEMPO, added during normoxic periods, depolarized membrane potential (severe hypoxia −73.6 to −61.4 mV, NAC −76.6 to −66.2 mV and MitoTEMPO −71.5 mV to −62.5 mV) and increased whole-cell conductance (severe hypoxia 5.7 nS to 8.0 nS, NAC 6.0 nS to 7.5 nS and MitoTEMPO 6.0 nS to 7.6 nS). Also, in a subset of active pyramidal neurons, these treatments reduced action potential firing frequency (severe hypoxia 0.18 Hz to 0.03 Hz, NAC 0.27 Hz to 0.06 Hz and MitoTEMPO 0.35 Hz to 0.08 Hz). Neither severe hypoxia nor ROS scavenging impacted action potential threshold. The addition of exogenous hydrogen peroxide could reverse the effects of the antioxidants. Taken together, this supports a role for a reduction in [ROS] as a low-oxygen signal in goldfish brain.
Mouse vocal emission and acoustic complexity do not scale linearly with the size of a social group
Authors: Warren Megan R. , Spurrier Morgan S. , Sangiamo Daniel T. , Clein Rachel S. , Neunuebel Joshua P.
Published: April 2021

Adult mice emit ultrasonic vocalizations (USVs), sounds above the range of human hearing, during social encounters. While mice alter their vocal emissions between isolated and social contexts, technological impediments have hampered our ability to assess how individual mice vocalize in group social settings. We overcame this challenge by implementing an 8-channel microphone array system, allowing us to determine which mouse emitted individual vocalizations across multiple social contexts. This technology, in conjunction with a new approach for extracting and categorizing a complex, full repertoire of vocalizations, facilitated our ability to directly compare how mice modulate their vocal emissions between isolated, dyadic and group social environments. When comparing vocal emission during isolated and social settings, we found that socializing male mice increase the proportion of vocalizations with turning points in frequency modulation and instantaneous jumps in frequency. Moreover, males change the types of vocalizations emitted between social and isolated contexts. In contrast, there was no difference in male vocal emission between dyadic and group social contexts. Female vocal emission, while predominantly absent in isolation, was also similar during dyadic and group interactions. In particular, there were no differences in the proportion of vocalizations with frequency jumps or turning points. Taken together, the findings lay the groundwork necessary for elucidating the stimuli underlying specific features of vocal emission in mice.
11-Deoxycortisol is a stress responsive and gluconeogenic hormone in a jawless vertebrate, the sea lamprey (Petromyzon marinus)
Authors: Shaughnessy Ciaran A. , McCormick Stephen D.
Published: April 2021

Although corticosteroid-mediated hepatic gluconeogenic activity in response to stress has been extensively studied in fishes and other vertebrates, there is little information on the stress response in basal vertebrates. In sea lamprey (Petromyzon marinus), a representative member of the most basal extant vertebrate group Agnatha, 11-deoxycortisol and deoxycorticosterone are the major circulating corticosteroids. The present study examined changes in circulating glucose and 11-deoxycortisol concentrations in response to a physical stressor. Furthermore, the gluconeogenic actions of 11-deoxycortisol and deoxycorticosterone were examined. Within 6 h of exposure of larval and juvenile sea lamprey to an acute handling stress, plasma 11-deoxycortisol levels increased 15- and 6-fold, respectively, and plasma glucose increased 3- and 4-fold, respectively. Radiometric receptor binding studies revealed that a corticosteroid receptor (CR) is present in the liver at lower abundance than in other tissues (gill and anterior intestine) and that the binding affinity of the liver CR was similar for 11-deoxycortisol and deoxycorticosterone. Transcriptional tissue profiles indicate a wide distribution of cr transcription, kidney-specific transcription of steroidogenic acute regulatory protein (star) and liver-specific transcription of phosphoenolpyruvate carboxykinase (pepck). Ex vivo incubation of liver tissue with 11-deoxycortisol resulted in dose-dependent increases in pepck mRNA levels. Finally, intraperitoneal administration of 11-deoxycortisol and deoxycorticosterone demonstrated that only 11-deoxycortisol resulted in an increase in plasma glucose. Together, these results provide the first direct evidence for the gluconeogenic activity of 11-deoxycortisol in an agnathan, indicating that corticosteroid regulation of plasma glucose is a basal trait among vertebrates.
Hard limits to cognitive flexibility: ants can learn to ignore but not avoid pheromone trails
Authors: Wenig Katharina , Bach Richard , Czaczkes Tomer J.
Published: April 2021

Learning allows animals to respond to changes in their environment within their lifespan. However, many responses to the environment are innate, and need not be learned. Depending on the level of cognitive flexibility an animal shows, such responses can either be modified by learning or not. Many ants deposit pheromone trails to resources, and innately follow such trails. Here, we investigated cognitive flexibility in the ant Lasius niger by asking whether ants can overcome their innate tendency and learn to avoid conspecific pheromone trails when these predict a negative stimulus. Ants were allowed to repeatedly visit a Y-maze, one arm of which was marked with a strong but realistic pheromone trail and led to a punishment (electric shock and/or quinine solution), and the other arm of which was unmarked and led to a 1 mol l−1 sucrose reward. After ca. 10 trials, ants stopped relying on the pheromone trail, but even after 25 exposures they failed to improve beyond chance levels. However, the ants did not choose randomly: rather, most ants began to favour just one side of the Y-maze, a strategy which resulted in more efficient food retrieval over time, when compared with the first visits. Even when trained in a go/no-go paradigm which precludes side bias development, ants failed to learn to avoid a pheromone trail. These results show rapid learning flexibility towards an innate social signal, but also demonstrate a rarely seen hard limit to this flexibility.
Novel Insights Into Biarticular Muscle Actions Gained From High-Density Electromyogram
Authors: Watanabe Kohei , Vieira Taian Martins , Gallina Alessio , Kouzaki Motoki , Moritani Toshio
Published: April 2021

Biarticular muscles have traditionally been considered to exhibit homogeneous neuromuscular activation. The regional activation of biarticular muscles, as revealed from high-density surface electromyograms, seems however to discredit this notion. We thus hypothesize the regional activation of biarticular muscles may contribute to different actions about the joints they span. We then discuss the mechanistic basis and methodological implications underpinning our hypothesis.
Estimating Exercise-Induced Changes in Human Neuronal Networks
Authors: Türker Kemal S.
Published: April 2021

Although several methods have been used to estimate exercise-induced changes in human neuronal networks, there are growing doubts about the methodologies used. This review describes a single motor unit–based method that minimizes the errors inherent in classical methods. With this method, it is now possible to identify human neuronal networks' changes due to exercise.
Wearable Monitors Facilitate Exercise in Adult and Pediatric Stem Cell Transplant
Authors: Pottebaum Ethan , Warmoth Alexa , Ayyappan Sabarish , Dickens David S. , Jethava Yogesh , Modi Arunkumar , Tomasson Michael H. , Carr Lucas J. , Bates Melissa L.
Published: April 2021

Hematopoietic stem cell transplant (HSCT) is a potentially curative treatment for hematopoietic malignancies, complicated by decreased performance status and quality of life. Exercise therapy improves outcomes in HSCT, but several barriers have prevented exercise from becoming routine clinical practice. Based on existing data that wearable technologies facilitate exercise participation in other sedentary and chronic illness populations, we propose the novel hypothesis that wearable technologies are a valuable tool in transcending barriers and developing exercise therapy programs for HSCT patients.
Heterogeneous Workers and Federal Income Taxes in a Spatial Equilibrium
Authors: Colas Mark , Hutchinson Kevin
Published: April 2021

We study the geographic incidence and efficiency of an income tax by estimating a spatial equilibrium model with heterogeneous workers. The US income tax shifts households out of high-productivity cities, leading to locational inefficiency of 0.25 percent of output. Removing spatial tax distortions increases inequality because more educated households are more mobile and own larger shares of land. Flattening the tax schedule, or introducing cost-of-living adjustments or local wage adjustments leads to efficiency gains but causes substantial increases in inequality. Differences in mobility and land ownership across skill groups create an equity-efficiency trade-off that is unique to spatial settings. (JEL H24, H22, D31, J31, J24, R23)
Highlights from the 2016-2020 NEUBIAS training schools for Bioimage Analysts: a success story and key asset for analysts and life scientists
Authors: Martins Gabriel G. , Cordelières Fabrice P. , Colombelli Julien , D’Antuono Rocco , Golani Ofra , Guiet Romain , Haase Robert , Klemm Anna H. , Louveaux Marion , Paul-Gilloteaux Perrine , Tinevez Jean-Yves , Miura Kota
Published: April 2021

NEUBIAS, the European Network of Bioimage Analysts, was created in 2016 with the goal of improving the communication and the knowledge transfer among the various stakeholders involved in the acquisition, processing and analysis of biological image data, and to promote the establishment and recognition of the profession of Bioimage Analyst. One of the most successful initiatives of the NEUBIAS programme was its series of 15 training schools, which trained over 400 new Bioimage Analysts, coming from over 40 countries. Here we outline the rationale behind the innovative three-level program of the schools, the curriculum, the trainer recruitment and turnover strategy, the outcomes for the community and the career path of analysts, including some success stories. We discuss the future of the materials created during this programme and some of the new initiatives emanating from the community of NEUBIAS-trained analysts, such as the NEUBIAS Academy. Overall, we elaborate on how this training programme played a key role in collectively leveraging Bioimaging and Life Science research by bringing the latest innovations into structured, frequent and intensive training activities, and on why we believe this should become a model to further develop in Life Sciences.
The existence and characteristics of rats and shrews in endemic leptospirosis areas and types of ectoparasites: a case study of West Jakarta, Indonesia
Authors: Susanna Dewi , Nova Rusyda Ihwani Tantia , Rozek Laura
Published: April 2021

Background: This study aimed to determine the presence and species of the rats and shrews that can potentially cause leptospirosis in West Jakarta, Indonesia, and the species of ectoparasites found in them.

Methods: The research was a descriptive study employing a cross-sectional approach. The study population was all species of rats and shrews in the region and the sample collection technique used was purposive sampling. The traps were installed in the homes of respondents who had suffered from leptospirosis and their closest neighbors, with a total of 521 traps. Leptospirosis data based on secondary data was obtained from West Jakarta Health Office (2016-August 2019). The technique for catching rats involved using humane live traps, while the identification of the rats and ectoparasites was done in the laboratory.

Results: It was found that more rats were caught in Cengkareng Timur sub-district, Cengkareng District, with a percentage of 14.8%, while the least in Duri Kepa, Kapuk, Kedaung Kali Angke and Kedoya Utara with a percentage of 3.7%. The rats were mostly found in East Cengkareng Sub-District, with the most common type being Rattus rattus (74.1 %) and the least Suncus murinus (11.1%); more male rats were caught (66.7%) than female (33.3%). The type of ectoparasite found in the rats was fleas. Xenopsylla cheopis was the most common type, at 83.3% and more fleas were male, at 66.7%. The most common rat species was Rattus rattus. The ectoparasite most commonly found in them was the female flea Xenopsylla cheopis.

Conclusions:  Rattus rattus and Xenopsylla cheopis were found in an East Cengkareng sub-district. Surveys, monitoring, and control of rats and ectoparasites are essential for the preparedness and development of an early warning system of possible diseases that they can cause.
Risk factors for major external structural birth defects among children in Kiambu County, Kenya: a case-control study
Authors: Agot George N. , Mweu Marshal M. , Wang'ombe Joseph K.
Published: April 2021

Background:Although major external structural birth defects continue to occur globally, the greatest burden is shouldered by resource-constrained countries with no surveillance systems. To our knowledge, many studies have been published on risk factors for major external structural birth defects, however, limited studies have been published in developing countries. The objective of this study was to identify risk factors for major external structural birth defects among children in Kiambu County, Kenya.

Methods:A hospital-based case-control study was used to identify the risk factors for major external structural birth defects. A structured questionnaire was used to gather information retrospectively on maternal exposure to environmental teratogens, multifactorial inheritance, and sociodemographic-environmental factors during the study participants' last pregnancies. 

Descriptive analyses (means, standard deviations, medians, and ranges) were used to summarize continuous variables, whereas categorical variables were summarized as proportions and percentages in frequency tables. Afterward, logistic regression analyses were conducted to estimate the effects of the predictors on the odds of major external structural birth defects in the country.

Results:Women who conceived when residing in Ruiru sub-county (adjusted odds ratio [aOR]: 5.28; 95% CI; 1.68-16.58; P<0.01), and Kiambu sub-county (aOR: 0.27; 95% CI; 0.076-0.95; P=0.04), and preceding siblings with history of birth defects (aOR: 7.65; 95% CI; 1.46-40.01; P=0.02) were identified as the significant predictors of major external structural birth defects in the county.

Conclusions:These findings pointed to MESBDs of genetic, multifactorial inheritance, and sociodemographic-environmental etiology. Thus, we recommend regional defect-specific surveillance programs, public health preventive measures, and treatment strategies to understand the epidemiology and economic burden of these defects in Kenya. We specifically recommend the integration of clinical genetic services with routine reproductive health services because of potential maternal genetic predisposition in the region.