bluuebunny/crossref_metadata_2025 huggingface dataset:
“You Can’t Go to War Over Refugees”: The Bangladesh War of 1971 and the International Refugee Regime
Authors: Biswas Bidisha
Published: January 2023

This article examines the 1971 refugee crisis between India and Pakistan and discusses its enduring lessons for the global refugee regime. The crisis, which drove an estimated ten million refugees into India within a space of nine months, led to a war between the two countries. The events of that year had significant geopolitical consequences. It led to the break-up of the Pakistani state, created the new country of Bangladesh, and involved the United Nations in one of its earliest, and largest, refugee repatriation campaigns. Yet, the case has received little attention in the refugee studies literature. Based on extensive archival research of the records of the US, British, and Indian governments, and of the office of the United Nations High Commissioner for Refugees, this article examines why and how the refugee crisis escalated into an interstate war. The study links the India–Pakistan case to ongoing challenges confronting the international refugee regime, particularly from the perspective of first-host countries. The 1971 crisis reminds us that refugee governance norms and practices must include more critical considerations of the conditions necessary to resolve forced migration situations.
Class Size and Learning: Has India Spent Too Much on Reducing Class Size?
Authors: Datta Sandip , Kingdon Geeta Gandhi
Published: January 2023

Whether class-size reductions improve student learning outcomes is an important policy question for India. This paper investigates the issue using a credible identification strategy to address the endogeneity of class size. Pupil fixed effects combined with value-added estimation show no significant relationship between class size and student achievement, which suggests that under current teaching practices, there is no learning gain from reducing class size. If these findings, based on a small sample in one city, hold true for the entire country, they have important policy implications. When generalized, our findings suggest that India experienced a value-subtraction from spending on reducing class sizes, and that the US$3.6 billion it spends annually on the salaries of the 0.4 million new teachers appointed between 2010 and 2017 is wasteful spending rather than an investment in improving learning. These findings imply that India could save US$19.4 billion per annum by increasing PTR to 40, without any reduction in pupil learning.
Topdressing Biochar Compost Mixtures and Biological Control Organism Applications Suppress Foliar Pathogens in Creeping Bentgrass Fairway Turf
Authors: Doherty Joseph R. , Roberts Joseph A.
Published: January 2023

Biochar, compost, and biological control agents can suppress pathogens on their own; however, their reliability and efficacy are not as acceptable as synthetic fungicides commonly used to suppress pathogens. A multiyear field study was initiated to evaluate combinations of monthly applications of a biochar compost mixture and weekly or biweekly Bacillus subtilis QST713 applications for their ability to suppress foliar pathogens on a creeping bentgrass (Agrostis stolonifera L.) fairway and to measure their impact on strain QST713 establishment. Disease severity and turfgrass quality were measured every 14 days throughout the growing season. Populations of strain QST713 were quantified by quantitative PCR analysis on DNA extracted from foliage samples collected throughout the trial. Biochar compost mixture applications increased turfgrass quality in both years of the study and reduced dollar spot (Clarireedia jacksonii Salgado-Salazar) severity in 2021. Weekly strain QST713 applications reduced copper spot (Gloeocercospora sorghi D. C. Bain & Edgerton) severity compared with biweekly applications and the nontreated control in 2020, yet monthly biochar compost mixture with weekly strain QST713 applications completely suppressed copper spot in 2021. Populations of strain QST713 were highest in weekly treated plots, and monthly biochar compost mixture applications did not affect strain QST713 establishment. Although there was not an interaction between biochar compost mixture and strain QST713 applications, implementing both in a season-long program will benefit turfgrass health and reduce disease severity.
Nematode-Suppressive Potential of Digestates to Meloidogyne incognita and Heterodera schachtii
Authors: Liu Ke , Eberlein Caroline , Edalati Abdelhossein , Zhang Ruihong , Westphal Andreas
Published: January 2023

Management of plant-parasitic nematodes uses host plant resistance, crop rotation, cultural methods, and nematicide applications. Host plant resistance is tedious to develop, and crop rotation and cultural methods are challenging to use. Environmental and human health concerns render sole reliance on chemical nematode suppression nonsustainable. Previously, digestate from anaerobically fermented maize silage suppressed Heterodera schachtii in Beta vulgaris crops. Here, seven digestates were investigated for nematode suppressive potential: liquid dairy manure digestate (LDMD), liquid dairy manure digestate with ammonia removed (LDMDA−), food waste digestate (FWD), liquid food waste digestate with ammonia removed (LFWDA−), liquid food waste digestate (LFWD), food waste hydrolysate from the Renewable Energy Anaerobic Digester (HREAD), and food waste hydrolysate from the South Area Transfer Station in Sacramento (HSATS). In a red radish (Raphanus sativus) bioassay with H. schachtii, digestates were amended at rates of 0.02, 0.11, 0.57, and 2.86 ml per 100 cm3 of soil. At a rate of 2.86 ml, all amendments except LDMDA− and LFWDA− significantly reduced juvenile root penetration compared with the infested control. In a greenhouse watermelon (Citrullus lanatus) bioassay with Meloidogyne incognita, amendments FWD, LFWD, HREAD, and HSATS as well as LDMD (less effectively) at 2.86 and 5.76 ml per 100 cm3 of soil significantly reduced egg masses per root system compared with the nontreated, nematode-infested control. In a microplot experiment with M. incognita and red radish, in the treatment amended with LFWD at 2.37 ml per 100 cm3 of soil, marketable yields were improved by approximately 50% over the nontreated control and were comparable with those in the treatment with the nematicide Reklemel. In a second microplot experiment with M. incognita and watermelon, treatments that contained LFWD at rates of 3.55 ml per 100 cm3 of soil had transient numerical effects of initial nematode suppression that were not maintained throughout the 3-month growth period. The results of these studies demonstrated that digestates FWD and LFWD consistently expressed some nematode-suppressive capacity.
Distinct effects of SDC3 and FGFRL1 on selective neurodegeneration in AD and PD
Authors: Wang Juelu , Chen Peiye , Hu Bolang , Cai Fang , Xu Qin , Pan Sipei , Wu Yili , Song Weihong
Published: January 2023

Alzheimer's disease (AD) and Parkinson's disease (PD) are age‐dependent neurodegenerative disorders. There is a profound neuronal loss in the basal forebrain cholinergic system in AD and severe dopaminergic deficiency within the nigrostriatal pathway in PD. Swedish APP (APPSWE) and SNCAA53T mutations promote Aβ generation and α‐synuclein aggregation, respectively, and have been linked to the pathogenesis of AD and PD. However, the mechanisms underlying selective cholinergic and dopaminergic neurodegeneration in AD and PD are still unknown. We demonstrated that APPSWE mutation enhanced Aβ generation and increased cell susceptibility to Aβ oligomer in cholinergic SN56 cells, whereas SNCAA53T mutations promoted aggregates formation and potentiated mutant α‐synuclein oligomer‐induced cytotoxicity in MN9D cells. Furthermore, syndecan‐3 (SDC3) and fibroblast growth factor receptor‐like 1 (FGFRL1) genes were differentially expressed in SN56 and MN9D cells carrying APPSWE or SNCAA53T mutation. SDC3 and FGFRL1 proteins were preferentially expressed in the cholinergic nucleus and dopaminergic neurons of APPSWE and SNCAA53T mouse models, respectively. Finally, the knockdown of SDC3 and FGFRL1 attenuated oxidative stress‐induced cell death in SN56‐APPSWE and MN9D‐SNCAA53T cells. The results demonstrate that SDC3 and FGFRL1 mediated the specific effects of APPSWE and SNCAA53T on cholinergic and dopaminergic neurodegeneration in AD and PD, respectively. Our study suggests that SDC3 and FGFRL1 could be potential targets to alleviate the selective neurodegeneration in AD and PD.
Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Childhood Autism-related Outcomes
Authors: Ames Jennifer L. , Burjak Mohamad , Avalos Lyndsay A. , Braun Joseph M. , Bulka Catherine M. , Croen Lisa A. , Dunlop Anne L. , Ferrara Assiamira , Fry Rebecca C. , Hedderson Monique M. , Karagas Margaret R. , Liang Donghai , Lin Pi-I D. , Lyall Kristen , Moore Brianna , Morello-Frosch Rachel , O’Connor Thomas G. , Oh Jiwon , Padula Amy M. , Woodruff Tracey J. , Zhu Yeyi , Hamra Ghassan B. ,   on behalf of program collaborators for Environmental influences on Child Health Outcomes
Published: January 2023

Background:

Epidemiologic evidence linking prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with altered neurodevelopment is inconclusive, and few large studies have focused on autism-related outcomes. We investigated whether blood concentrations of PFAS in pregnancy are associated with child autism-related outcomes.

Methods:

We included 10 cohorts from the National Institutes of Health (NIH)-funded Environmental influences on Child Health Outcomes (ECHO) program (n = 1,429). We measured 14 PFAS analytes in maternal blood collected during pregnancy; eight analytes met detection criteria for analysis. We assessed quantitative autism-related traits in children via parent report on the Social Responsiveness Scale (SRS). In multivariable linear models, we examined relationships of each PFAS (natural log-transformed) with SRS scores. We further modeled PFAS as a complex mixture using Bayesian methods and examined modification of these relationships by child sex.

Results:

Most PFAS in maternal blood were not associated with child SRS T-scores. Perfluorononanoic acid (PFNA) showed the strongest and most consistent association: each 1-unit increase in ln-transformed PFNA was associated with greater autism-related traits (adjusted β [95% confidence interval (CI)] = 1.5 [–0.1, 3.0]). The summed mixture, which included six PFAS detected in >70% of participants, was not associated with SRS T-scores (adjusted β [95% highest posterior density interval] = 0.7 [–1.4, 3.0]). We did not observe consistent evidence of sex differences.

Conclusions:

Prenatal blood concentrations of PFNA may be associated with modest increases in child autism-related traits. Future work should continue to examine the relationship between exposures to both legacy and emerging PFAS and additional dimensional, quantitative measures of childhood autism-related outcomes.
Asbestos-associated pulmonary disease
Authors: Caceres Jose Diego , Venkata Anand N.
Published: January 2023

Purpose of review

Exposure to asbestos can cause both benign and malignant, pulmonary and pleural diseases. In the current era of low asbestos exposure, it is critical to be aware of complications from asbestos exposure; as they often arise after decades of exposure, asbestos-related pulmonary complications include asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and malignant pleural mesothelioma.

Recent findings

Multiple recent studies are featured in this review, including a study evaluating imaging characteristics of asbestos with other fibrotic lung diseases, a study that quantified pleural plaques on computed tomography imaging and its impact on pulmonary function, a study that examined the risk of lung cancer with pleural plaques among two large cohorts and a review of nonasbestos causes of malignant mesothelioma.

Asbestos-related pulmonary and pleural diseases continue to cause significant morbidity and mortality. This review summarizes the current advances in this field and highlights areas that need additional research.
Predicting Outdoor Walking 1 Year After Spinal Cord Injury: A Retrospective, Multisite External Validation Study
Authors: Draganich Christina , Weber Kenneth A. , Thornton Wesley A. , Berliner Jeffrey C. , Sevigny Mitch , Charlifue Susan , Tefertiller Candace , Smith Andrew C.
Published: January 2023

Background and Purpose:

Predicting future outdoor walking ability after spinal cord injury (SCI) is important, as this is associated with community engagement and social participation. A clinical prediction rule (CPR) was derived for predicting outdoor walking 1 year after SCI. While promising, this CPR has not been validated, which is necessary to establish its clinical value. The objective of this study was to externally validate the CPR using a multisite dataset.

Methods:

This was a retrospective analysis of US SCI Model Systems data from 12 centers. L3 motor score, L5 motor score, and S1 sensory score were used as predictor variables. The dataset was split into testing and training datasets. The testing dataset was used as a holdout dataset to provide an unbiased estimate of prediction performance. The training dataset was used to determine the optimal CPR threshold through a “leave-one-site-out” cross-validation framework. The primary outcome was self-reported outdoor walking ability 1 year after SCI.

Results:

A total of 3721 participants' data were included. Using the optimal CPR threshold (CPR ≥ 33 threshold value), we were able to predict outdoor walking 1 year with high cross-validated accuracy and prediction performance. For the entire dataset, area under receiver operator characteristic curve was 0.900 (95% confidence interval: 0.890-0.910; P < 0.0001).

Discussion and Conclusions:

The outdoor walking CPR has been externally validated. Future research should conduct a clinical outcomes and cost-benefit impact analysis for implementing this CPR. Our results support that clinicians may use this 3-variable CPR for prediction of future outdoor walking ability.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A411).
Estimated Number of Incident HIV Infections in Men Who Have Sex With Men Attributable to Gonorrhea and Chlamydia, Per Gonococcal or Chlamydial Infection, in the United States
Authors: Jones Jeb , Jenness Samuel M. , Le Guillou Adrien , Sullivan Patrick S. , Gift Thomas L. , Delaney Kevin P. , Chesson Harrell
Published: January 2023

Using a network modeling approach, we estimate that the probability of a sexually transmitted infection–attributable HIV infection among men who have sex with men is 0.44% per gonococcal or chlamydial infection.

Using a network model, we simulated transmission of HIV, gonorrhea, and chlamydia among men who have sex with men to estimate the number of HIV infections that can be attributed to gonorrhea and chlamydia, per gonococcal and chlamydial infection. This metric can inform future modeling and health economic studies.
Use of Obstetric and Gynecologic Hospitalists Is Associated With Decreased Severe Maternal Morbidity in the United States
Authors: Torbenson Vanessa E. , Tatsis Vasiliki , Bradley Sarah L. , Butler Jennifer , Kjerulff Lucy , McLaughlin G. Blake , Stika Catherine S. , Tappin Dyanne , VanBlaricom Amy , Mehta Ramila , Branda Megan , McCue Brigid
Published: January 2023

Objectives

This study aimed to evaluate the prevalence of obstetric and gynecologic (Ob/Gyn) hospitalists and determine if an association exists between the presence of Ob/Gyn hospitalists and severe maternal morbidity (SMM).

Methods

This observational study included data from hospitals listed in the USA TODAY’s 2019 article titled, “Deadly deliveries: Childbirth complication rates at maternity hospitals.” Telephone and email surveys of staff in these hospitals identified the presence or absence of continuous providers in the hospital 24 hours, 7 days a week (24/7 coverage) and the types of providers who are employed, then compared these responses with the SMM cited by USA TODAY.

Results

Eight hundred ten hospitals were contacted, with participation from 614 labor and delivery units for a response rate of 75.8%. Fifty-seven percent of units were staffed with 24/7 coverage, with 46% of hospitals’ coverage primarily provided by an Ob/Gyn hospitalist and 54% primarily by a nonhospitalist OB/Gyn provider. The SMM and presence of 24/7 coverage increased with the level of neonatal care and delivery volume. Of hospitals with 24/7 coverage, those that primarily used Ob/Gyn hospitalists had a lower SMM for all mothers (1.7 versus 2.0, P = 0.014) and for low-income mothers (1.9 versus 2.30, P = 0.007) than those who primarily used nonhospitalist OB/Gyn providers.

Conclusions

Severe maternal morbidity increases with delivery volume, level of neonatal care, and 24/7 coverage. Of hospitals with 24/7 coverage, units that staff with Ob/Gyn hospitalists have lower levels of SMM than those that use nonhospitalist Ob/Gyn providers.
Footwear limitations in women prosthesis users relate to more than preference
Authors: Russell Esposito Elizabeth , Hansen Andrew H. , Slater Billie Savvas , Major Matthew J. , Muschler Katherine , Ikeda Andrea J. , Erbes Christopher
Published: January 2023

Background:

The option to wear desired footwear may be an important part of community reintegration after lower-limb amputation.

Objectives:

This study explored outcomes related to footwear, health, and participation in women Veterans with lower-limb amputation.

Methods:

A cross-sectional questionnaire was mailed to all women Veterans age 18–82 years with major lower-limb amputation(s) who had received prosthetics services in the US Department of Veterans Affairs (N = 538). The questionnaire assessed Perceived Challenges (including clothing limitations, prosthetic foot limitations [width, height, and shape], and shoe avoidance for safety concerns), type of footwear used and preference, and included subscales from the Patient-Reported Outcome Measurement Information System, Amputee Body Image Scale Prosthetic Limb Users' Survey of Mobility, Community Participation Index, Activities-Specific Balance Confidence Scale, and Prosthesis Evaluation Questionnaire. Bivariate correlations examined relationships between a composite measure of Perceived Challenges and patient-reported outcomes.

Results:

One hundred questionnaires were returned (18.6% response rate; 3 excluded for limited prosthesis use). The Perceived Challenges score was significantly correlated with scores for the Amputee Body Image Scale—Revised (r = 0.24, p = 0.019), Patient-Reported Outcome Measurement Information System (ability to participate: r = −0.25, p = 0.014), Prosthesis Evaluation Questionnaire (utility: r = −0.32, p = 0.001, appearance: r = −0.48, p < 0.001), Activities-Specific Balance Confidence Scale (r = −0.20, p = 0.046), and Prosthetic Limb Users' Survey of Mobility (r = −0.21, p = 0.036), but not depression or anxiety.

Conclusions:

Women who have greater issues with how their prosthesis affects the shoes and clothing they can wear also have poorer body image, reduced functional capabilities, and lower reported participation in activities. Improved prosthetic foot design may help to improve social participation and other important outcomes for women prosthesis users.
Port-Site Metastasis Identified on Prostate-Specific Membrane Antigen–Targeted 18F-DCFPyL PET/CT After Robot-Assisted Laparoscopic Radical Prostatectomy
Authors: Zahed Hanan , Laufer Jerome , LeBlanc Martin , Tisseverasinghe Steven , Niazi Tamim , Probst Stephan
Published: January 2023

Port-site metastasis is an extremely rare complication following minimally invasive oncologic surgery for prostate cancer. We present the case of a 74-year-old man who underwent robot-assisted laparoscopic radical prostatectomy followed by salvage radiotherapy. Despite treatment, he developed biochemical recurrence. However, there was no evidence of disease on CT and bone scan at a prostate-specific antigen of 4.6 ng/mL. Subsequently, 18F-DCFPyL PET/CT revealed a solitary focus of intense uptake in the right rectus abdominis muscle that was felt to represent a port-site metastasis. Histopathologic evaluation with immunostaining following ultrasound-guided needle biopsy confirmed the presence of metastatic adenocarcinoma of the prostate.
Lung Ventilation-Perfusion Scan in COVID-19
Authors: Karamian Farivash , Sadeghi Ramin , Askari Emran
Published: January 2023

Although COVID-19 infection is associated with the increased risk of pulmonary thromboembolism (PTE), COVID-19 pulmonary lesions cause ventilation-perfusion (V/Q) patterns other than PTE. Although extensive research has been done to address different anatomical patterns of COVID-19, there is a knowledge gap in terms of V/Q lung scintigraphy in these patients. The purpose of this study is to demonstrate these patterns and to show how important it is to use SPECT/CT in addition to planar images to differentiate between these patterns from PTE. In the current collection, we presented various patterns of V/Q SPECT/CT abnormalities in COVID-19 patients.
Evaluation of High-Interval Education to Improve Outcomes for Bariatric Patients With Health Disparities
Authors: Sykora Laura Addison , Yoder Angela Collins , Richards William O.
Published: January 2023

A correlation of health disparities, socioeconomic barriers, and health literacy were hypothesized as causative factors of poor weight loss, weight regain, and loss to clinical follow-up in postbariatric patients. This study explored nurse practitioner-led interventions to address health disparities and improve outcomes. This pilot project evaluated 3-month weights of an intervention cohort as compared with a retrospective cohort. The intervention cohort received a weekly educational phone call from the clinical nurse practitioner. Quantitative data based on 3-month weights reveal an average excess body weight percentage lost at the 3-month postoperative clinical visit (36.54 ± 0.11, p = .2929) in the retrospective cohort (n = 30) as compared with the intervention cohort (n = 30; 33.46 ± 0.11, p = .2929). Participants responding to the barriers screening tool did not correspond with the actual needs represented by the population. Food access and transportation were leading factors affecting weight loss. This project revealed implications including the need for development of bariatric-specific social needs assessments, the need to explore telehealth as a modality to improve patient education, the need to modify education to overcome deficits in health literacy. Findings also validate the role of the nurse practitioner as a leader of multidisciplinary care teams.
Nonneurologic causes of binocular diplopia for the neurologist
Authors: Mosleh Rasha , Peragallo Jason H.
Published: January 2023

Purpose of review

To review several etiologies of nonneurologic diplopia that the neurologist should be familiar with. The pathophysiology, clinical presentation, neuroimaging findings, and treatment options are briefly summarized for each condition.

Recent findings

Certain etiologies for diplopia can be associated with life-threatening neurologic conditions and should be investigated thoroughly for proper localization and immediate management of the underlying disease. However, nonneurological causes of binocular diplopia are very common and disabling, but are often nonemergent and may not require in-depth investigation or neuroimaging. Some of the etiologies of nonneurologic diplopia mimic cranial nerve palsies, making them confusing to evaluate when the physician is not familiar with these etiologies. Unfamiliarity with these diagnoses can lead to unnecessary neuroimaging, inefficient utilization of medical resources, and undue alarm to the patient. Recent advances in clinical diagnostic tools and neuroimaging have clarified our understanding of the diverse underlying mechanisms of nonneurologic binocular diplopia.

Diplopia can be a difficult symptom for the neurologist to evaluate. A systematic approach to the evaluation of diplopia can help establish the urgency and necessity of an extensive workup.

This review will help to familiarize the neurologist with nonneurological causes of binocular diplopia, minimize expensive and unnecessary evaluations, and reassure patients and physicians alike.
Heterogeneous distribution of sex ratio distorters in natural populations of the isopod
Armadillidium vulgare
Authors: Durand Sylvine , Lheraud Baptiste , Giraud Isabelle , Bech Nicolas , Grandjean Frédéric , Rigaud Thierry , Peccoud Jean , Cordaux Richard
Published: January 2023

In the isopod
Armadillidium vulgare
, many females produce progenies with female-biased sex ratios, owing to two feminizing sex ratio distorters (SRD):
Wolbachia
endosymbionts and the
f
element. We investigated the distribution and population dynamics of these SRD and mitochondrial DNA variation in 16 populations from Europe and Japan. Confirming and extending results from the 1990s, we found that the SRD are present at variable frequencies in populations and that the
f
element is overall more frequent than
Wolbachia
. The two SRD never co-occur at high frequency in any population, suggesting an apparent mutual exclusion. We also detected
Wolbachia
or the
f
element in some males, which probably reflects insufficient titer to induce feminization or presence of masculinizing alleles. Our results are consistent with a single integration event of a
Wolbachia
genome in the
A. vulgare
genome at the origin of the
f
element, which contradicts an earlier hypothesis of frequent losses and gains. We identified strong linkage between
Wolbachia
strains and mitochondrial haplotypes, but no association between the
f
element and mitochondrial background. Our results open new perspectives on SRD evolutionary dynamics in
A. vulgare
, the evolution of genetic conflicts and their impact on the variability of sex determination systems.
Building case investigation and contact tracing programs in U.S. state and local health departments: a conceptual framework
Authors: Woodward Alexandra , Rivers Caitlin
Published: January 2023

The COVID-19 pandemic and earlier health events have demonstrated that when effectively implemented, case investigation and contact tracing (CI/CT) can break chains of transmission by promptly identifying, quarantining, and monitoring the contacts of infected cases, thereby limiting further spread of a disease in a community. Many public health experts agree that implementing CI/CT at the early stages of an outbreak can be an extremely effective approach to controlling an outbreak; as such, health departments must have CI/CT capacities in place prior to the detection of an outbreak to ensure readiness to respond. At the onset of the COVID-19 pandemic, and to this day, U.S. state and local public health departments lack comprehensive CI/CT guidelines that clearly define the capabilities, capacities, outcomes, and impacts of CI/CT programs. This research has resulted in the first comprehensive analysis of the goals, capabilities, and capacities of CI/CT programs, as well as a conceptual framework that represents the relationships between these program components and considerations. Our findings highlight the need for further guidance to assist U.S. state and local public health departments in shifting CI/CT program goals as outbreaks evolve. Moreover, training the public health workforce on making decisions around CI/CT program implementation during evolving outbreaks is critical to ensure readiness to respond to a variety of outbreak scenarios.
Effect of preoperative educational counselling about routine elements of peri-operative care on patient’s experience through their first surgical journey: a randomised control trial
Authors: Kurian Feba Susan , Balakrishnan Santosh , Jojo Joicy Els
Published: January 2023

AIM

To investigate whether pre-operative counselling about non-procedural elements of perioperative care improves patient’s overall surgical experience, through their first surgical journey

OBJECTIVE

To study the effect pre-operative counselling about non-procedural elements of perioperative care in a tertiary care centre, on the care experience of such patients.

METHODS

62 Patients charted for their first-ever surgical procedure, were enrolled for the trial giving an Interventional group (A: n= 32) and control group (B: n = 30). Surgical experience was recorded 48 hours after surgery on regional-language questionnaire, developed & validated by an expert group. Data was compiled in Ms Excel and Statistical analysis was done using R software.

RESULTS

Mean scores were compared with paired T-test. Groups A and B had a mean experience score of 71.78 and 62.93 respectively (Mean difference (MD) 8.85; P <0.001). Mean scores in preoperative, intraoperative & post-operative domains were 33.31 vs 30.27 (MD 3.05; P <0.001), 14.47 versus 12.30 (MD 2.15; P <0.001) and 24.00 vs 20.37 (MD 3.63; P <0.001) for the groups respectively.

There was significant difference in surgical experience scores favouring the interventional group who recorded greater confidence and satisfaction with overall surgical experience and also separately for preoperative, intraoperative and postoperative periods.

CONCLUSION

Educating patients undergoing their first surgery about elements of perioperative care inherent to hospitalization for any surgery, has significant role in improving patients’ overall care experience in their surgical journey. Regularising such practice could improve overall surgical experience for patients.
Compassion training influences state but not trait level heart-rate variability within severe depression
Authors: Kim Jeffrey J. , Sherwell Chase , Kirby James N.
Published: January 2023

Heart-rate variability (HRV) is a marker of parasympathetic nervous system activity, and is a robust predicter of improved mental and physical health. Current psychotherapeutic interventions are effective at reducing self-report depressive symptoms, but few have improved HRV within a sample of severe depressive symptoms. This study explores the impact of a brief Compassion Focused Therapy exercise (CFT) on HRV. Results suggested that a brief CFT exercise can successfully target depressive physiology, at two distinct timepoints, pre- and post-a two-week self-directed training period. Specifically, we first show that CFT can significantly improve HRV at the state level, but not at the trait level after a two-week intervention. Second, CFT can increase a subset of participants’ HRV above a clinical cut-off of low resting HRV. Third, the frequency of practice (i.e., listening to the audio recording) during the self-directed training component was very low, with 50% not accessing the practice. Finally, during the CFT exercise at post-two-week training HRV decreased across time, indicating participants had a greater engagement in the ‘threat’ component of the CFT exercise – a feature to be more fully examined in prospective studies. This study suggests the value of future research with larger-scale randomized control trials, to further explore the modulation of parasympathetic physiology using compassion practices.
Cytotoxic CNS-associated T cells drive axon degeneration by targeting perturbed myelinating oligodendrocytes inPLP1mutant mice
Authors: Abdelwahab Tassnim , Stadler David , Knöpper Konrad , Arampatzi Panagiota , Saliba Antoine-Emmanuel , Kastenmüller Wolfgang , Martini Rudolf , Groh Janos
Published: January 2023

Myelin defects lead to neurological dysfunction in various diseases and in normal aging. Chronic neuroinflammation often contributes to axon-myelin damage in these conditions and can be initiated and/or sustained by perturbed myelinating glia. We have previously shown that distinct mutations in thePLP1gene result in neurodegeneration that is largely driven by adaptive immune cells. Here we characterize CD8+CNS-associated T cells in these myelin mutants using single-cell transcriptomics and identify population heterogeneity and disease-associated changes. We demonstrate that early sphingosine-1-phosphate receptor modulation attenuates the recruitment of T cells and neural damage, while later targeting of CNS-associated T cell populations is inefficient and has no effect on neurodegeneration. Applying bone marrow chimerism and utilizing random X chromosome inactivation, we provide evidence that axonal damage is driven by cytotoxic, antigen specific CD8+T cells that target mutant myelinating oligodendrocytes. These findings offer insights into neural-immune interactions and are of translational relevance for neurological conditions associated with myelin defects and neuroinflammation.
Physical mechanisms of red blood cell splenic filtration
Authors: Moreau Alexis , Yaya François , Lu Huijie , Surendranath Anagha , Charrier Anne , Dehapiot Benoit , Helfer Emmanuèle , Viallat Annie , Peng Zhangli
Published: January 2023

The splenic interendothelial slits fulfill the essential function of continuously filtering red blood cells (RBCs) from the bloodstream to eliminate abnormal and aged cells. To date, the process by which 8 µm RBCs pass through 0.3 µm-wide slits remains enigmatic. Does the slit caliber increase during RBC passage as sometimes suggested? Here, we elucidated the mechanisms that govern the RBC retention or passage dynamics in slits by combining multiscale modeling, live imaging, and microfluidic experiments on an original device with sub-micron wide physiologically calibrated slits. We observed that healthy RBCs pass through 0.28 µm-wide rigid slits at 37°C. To achieve this feat, they must meet two requirements. Geometrically, their surface area-to-volume ratio must be compatible with a shape in two tether-connected equal spheres. Mechanically, the cells with a low surface area-to-volume ratio (28 % of RBCs in a 0.4 µm-wide slit) must locally unfold their spectrin cytoskeleton inside the slit. In contrast, activation of the mechanosensitive PIEZO1 channel is not required. The RBC transit time through the slits follows a -1 and -3 power law with in-slit pressure drop and slip width, respectively. This law is similar to that of a Newtonian fluid in a 2D Poiseuille flow, showing that the dynamics of RBCs is controlled by their cytoplasmic viscosity. Altogether, our results show that filtration through submicron-wide slits is possible without further slit opening. Furthermore, our approach addresses the critical need for in-vitro evaluation of splenic clearance of diseased or engineered RBCs for transfusion and drug delivery.

Significance Statement

Splenic filtration of red blood cells through narrow interendothelial slits remains poorly understood despite its physiological significance as experiments and imaging of red cells passing through the slits are lacking. Here, we coupled live imaging, biomimetic submicron-fluidics, and multiscale modeling to quantify passage conditions. Remarkably, healthy 8-µm cells can pass through 0.28-µm slits at body temperature. This event is conditioned to cells being able to deform into two tether-connected equal spheres and, in limiting cases, to unfold their spectrin cytoskeleton. We showed that cells behave like a Newtonian fluid and that their dynamics is controlled by the inner fluid viscosity. We thus propose an in-vitro and in-silico approach to quantify splenic clearance of diseased cells and cells engineered for transfusion and drug delivery.
Tissue-specific sex difference in mouse eye and brain metabolome under fed and fasted states
Authors: Saravanan Meghashri , Xu Rong , Roby Olivia , Wang Yekai , Zhu Siyan , Lu Amy , Du Jianhai
Published: January 2023

Purpose

Visual physiology and various ocular diseases demonstrate sexual dimorphisms; however, how sex influences metabolism in different eye tissues remains undetermined. This study aims to address common and tissue-specific sex differences in metabolism in the retina, retinal pigment epithelium (RPE), lens and brain under fed and fasted conditions.

Methods

After ad libitum fed or deprived of food for 18 hours, mouse eye tissues (retina, RPE/choroid, and lens), brain, and plasma were harvested for targeted metabolomics. The data were analyzed with both Partial least squares-discriminant analysis (PLS-DA) and Volcano Plot analysis.

Results

Among 133 metabolites that cover major metabolic pathways, we found 9-45 metabolites that are sex-different in different tissues under the fed state and 6-18 metabolites under the fasted state. Among these sex-different metabolites, 33 were changed in two or more tissues, and 64 were tissue-specific. Pantothenic acid, hypotaurine and 4-hydroxyproline were the top commonly changed metabolites. Lens and retina had the most tissue-specific sex-different metabolites enriched in the metabolism of amino acid, nucleotide, lipids and TCA cycle. Lens and brain had more similar sex-different metabolites than other occular tissues. Female RPE and female brain were more sensitive to fasting with more reduced metabolites in amino acid metabolism, TCA cycle and glycolysis. The plasma had the least sex-different metabolites with very few overlapping changes with tissues.

Conclusion

Sex has a strong influence on eye and brain metabolism in tissue-specific and metabolic state-specific manners. Our findings may implicate the sexual dimorphisms in eye physiology and susceptibility to ocular diseases.
Associative white matter tracts selectively predict sensorimotor learning
Authors: Vinci-Booher S. , McDonald D.J. , Berquist E. , Pestilli F.
Published: January 2023

Human learning is a complex phenomenon that varies greatly among individuals and is related to the microstructure of major white matter tracts in several learning domains, yet the impact of the existing myelination of white matter tracts on future learning outcomes remains unclear. We employed a machine-learning model selection framework to evaluate whether existing microstructure might predict individual differences in the potential for learning a sensorimotor task, and further, if the mapping between the microstructure of major white matter tracts and learning was selective for learning outcomes. We used diffusion tractography to measure the mean fractional anisotropy (FA) of white matter tracts in 60 adult participants who then underwent training and subsequent testing to evaluate learning. During training, participants practiced drawing a set of 40 novel symbols repeatedly using a digital writing tablet. We measured drawing learning as the slope of draw duration over the practice session and visual recognition learning as the performance accuracy in an old/new 2-AFC recognition task. Results demonstrated that the microstructure of major white matter tracts selectively predicted learning outcomes, with left hemisphere pArc and SLF 3 tracts predicting drawing learning and the left hemisphere MDLFspl predicting visual recognition learning. These results were replicated in a repeat, held-out data set and supported with complementary analyses. Overall, results suggest that individual differences in the microstructure of human white matter tracts may be selectively related to future learning outcomes and open avenues of inquiry concerning the impact of existing tract myelination in the potential for learning.

Significance statement

A selective mapping between tract microstructure and future learning has been demonstrated in the murine model and, to our knowledge, has not yet been demonstrated in humans. We employed a data-driven approach that identified only two tracts, the two most posterior segments of the arcuate fasciculus in the left hemisphere, to predict learning a sensorimotor task (drawing symbols) and this prediction model did not transfer to other learning outcomes (visual symbol recognition). Results suggest that individual differences in learning may be selectively related to the tissue properties of major white matter tracts in the human brain.
Comprehensive approach to study branched ubiquitin chains reveals roles for K48-K63 branches in VCP/p97-related processes
Authors: Lange Sven M. , McFarland Matthew R. , Lamoliatte Frederic , Kwaśna Dominika , Shen Linnan , Wallace Iona , Cole Isobel , Armstrong Lee A. , Knebel Axel , Johnson Clare , De Cesare Virginia , Kulathu Yogesh
Published: January 2023

Branched ubiquitin (Ub) chains make up a significant proportion of Ub polymers in human cells and are formed when two or more sites on a single Ub molecule are modified with Ub creating bifurcated architectures. Despite their abundance, we have a poor understanding of the cellular functions of branched Ub signals that stems from a lack of facile tools and methods to study them. Here we develop a comprehensive pipeline to define branched Ub function, using K48-K63-branched chains as a case study. We discover branch-specific binders and, by developing a method that monitors cleavage of linkages within complex polyUb, we discover the VCP/p97-associated ATXN3, and MINDY family deubiquitinases to act as debranching enzymes. By engineering and utilizing a branched K48-K63-Ub chain-specific nanobody, we reveal roles for these chains in VCP/p97-related processes. In summary, we provide a blueprint to investigate branched Ub function that can be readily applied to study other branched chain types.

Highlights

Assembly of defined branched ubiquitin chains enables identification of specific binding proteins

Development of quantitative DUB assay monitoring cleavage of individual Ub linkages within complex ubiquitin chains identifies debranching enzymes

Engineering specific, high-affinity nanobody against branched K48-K63 ubiquitin reveals roles in VCP/p97 related processes and DNA damage responses

General blueprint of new methods and tools for in-depth characterization of branched ubiquitin chains and their underlying biology
Uncovering the Dynamics of Precise Repair at CRISPR/Cas9-induced Double-Strand Breaks
Authors: Ben-Tov Daniela , Mafessoni Fabrizio , Cucuy Amit , Honig Arik , Melamed-Bessudo Cathy , Levy Avraham A.
Published: January 2023

CRISPR/Cas9-mediated genome editing relies on error-prone repair of targeted DNA double-strand breaks (DSBs). Understanding CRISPR/Cas9-mediated DSB induction and subsequent repair dynamics requires measuring the rate of cutting and that of precise repair, a hidden-variable of the repair machinery. Here, we present a molecular and computational toolkit for multiplexed quantification of DSB intermediates and repairproducts by single-molecule sequencing. Using this approach, we characterized the dynamics of DSB induction, processing and repair at endogenous loci along a 72-hour time-course in tomato protoplasts. Combining this data with kinetic modeling reveals that indel accumulation is not an accurate reflection of DSB induction efficiency due to prominent precise re-ligation, accounting for 40-70% of all repair events. Altogether, this system exposes previously unseen flux in the DSB repair process, decoupling induction and repair dynamics, and suggesting an essential role of high-fidelity repair in limiting CRISPR editing efficiency in somatic cells.
Trade-offs between cost and information in cellular prediction
Authors: Tjalma Age J. , Galstyan Vahe , Goedhart Jeroen , Slim Lotte , Becker Nils B. , ten Wolde Pieter Rein
Published: January 2023

Living cells can leverage correlations in environmental fluctuations to predict the future environment and mount a response ahead of time. To this end, cells need to encode the past signal into the output of the intracellular network from which the future input is predicted. Yet, storing information is costly while not all features of the past signal are equally informative on the future input signal. Here, we show, for two classes of input signals, that cellular networks can reach the fundamental bound on the predictive information as set by the information extracted from the past signal: pushpull networks can reach this information bound for Markovian signals, while networks that take a temporal derivative can reach the bound for predicting the future derivative of non-Markovian signals. However, the bits of past information that are most informative about the future signal are also prohibitively costly. As a result, the optimal system that maximizes the predictive information for a given resource cost is, in general, not at the information bound. Applying our theory to the chemotaxis network ofEscherichia colireveals that its adaptive kernel is optimal for predicting future concentration changes over a broad range of background concentrations, and that the system has been tailored to predicting these changes in shallow gradients.
miRCurator: A rapid curation and analysis tool for plant microRNA studies
Authors: Avşar Bihter , Aliabadi Danial Esmaeili
Published: January 2023

Plant microRNAs (miRNAs) are tiny, non-coding RNAs that regulate the biological pathways either by inducing translational repression or messenger RNA decay. The advent of sequencing technologies increases the number of biological tools and computational methods to identify miRNAs with their targets inside the genome and transcriptome. In this study, we present a rapid curation software tool, the so-calledmiRCurator, which filters out unwanted microRNA candidates based on three significant criteria: (1) the pre-miRNA sequence should be deprived of multi-branched loops; (2) less than four mismatches on between mature miRNA and miRNA* strand are allowed; (3) no mismatches at DICER cut points are permitted on a mature miRNA strand.miRCuratoris a stand-alone user-friendly package that does not rely on cutting-edge computing platforms. We have examined our tool on different organisms, which are shown as case studies, and it was able to successfully identify all the unwanted miRNA candidates. The developed tool helps to identify genuine miRNAs and provides reliable outcomes in an automated fashion by eliminating false-positive predictions.
Evidence for an RNAi-independent role of DICER-LIKE2 in conferring growth inhibition and basal antiviral resistance
Authors: Nielsen Carsten Poul Skou , Arribas-Hernández Laura , Han Lijuan , Andersen Stig Uggerhøj , Pumplin Nathan , Brodersen Peter
Published: January 2023

Higher plants encode four DICER-LIKE (DCL) enzymes responsible for the production of small non-coding RNAs which function in RNA interference (RNAi). Different RNAi pathways in plants effect transposon silencing, antiviral defense and endogenous gene regulation.DCL2acts genetically redundantly withDCL4to confer basal antiviral defense, but in other settings,DCL2has the opposite function ofDCL4, at least in formal genetic terms. For example, knockout ofDCL4causes growth defects that are suppressed by inactivation ofDCL2. Current models maintain that the biochemical basis of both of these effects is RNAi via DCL2-dependent small interfering RNAs (siRNAs). Here, we report that neither DCL2-mediated antiviral resistance nor growth defects can be explained by silencing effects of DCL2-dependent siRNAs. Both functions are defective in genetic backgrounds that maintain high levels of DCL2-dependent siRNAs, either through specific point mutations in DCL2 or simply by reducing DCL2 dosage in plants heterozygous fordcl2knockout alleles. Intriguingly, however, all functions of DCL2 depend on it having some level of catalytic activity. We discuss this requirement for catalytic activity, but not for the resulting siRNAs, in the light of recent findings that reveal a function of DCL2 in activation of innate immunity in response to cytoplasmic double-stranded RNA.