bluuebunny/crossref_metadata_2025 huggingface dataset:
Covid-19 impact on food insecurity in Uganda: a dynamic analysis
Authors: Ubabukoh Chisom L. , Tampubolon Gindo
Published: March 2023

Lockdowns were used as a tool to avoid excessive social contact and thus limit the spread of Covid-19. However, the true welfare effects of this policy action are still being determined. This paper studies the impact of these lockdowns on the food security outcomes of households in Uganda using a dynamic probit model. We find that the most consequential determinant of whether a household’s food security was severely impacted by the lockdown was the initial status of whether a family was food insecure to begin with. Also, an increase in a household’s economic resources (log consumption per person) significantly influences a reduction in the probability of being severely food insecure. Over time, this creates a wedge of greater inequality between the food security of households who were initially food secure and those who were not. This is despite the use of government cash transfers which have turned out to be ineffective.

Highlights

A dynamic probit model is used to assess the influence Covid lockdowns have had on food security

Households who were initially severely food insecure experienced greater levels of food insecurity post-lockdown, than those who were not.

Increased command of economic resources reduces the probability of severe food security

Contemporaneous government transfers have not made a significant impact on reducing the probability of severe food insecurity
Microbiome Preterm Birth DREAM Challenge: Crowdsourcing Machine Learning Approaches to Advance Preterm Birth Research
Authors: Golob Jonathan L. , Oskotsky Tomiko T. , Tang Alice S. , Roldan Alennie , Chung Verena , Ha Connie W.Y. , Wong Ronald J. , Flynn Kaitlin J. , Parraga-Leo Antonio , Wibrand Camilla , Minot Samuel S. , Andreoletti Gaia , Kosti Idit , Bletz Julie , Nelson Amber , Gao Jifan , Wei Zhoujingpeng , Chen Guanhua , Tang Zheng-Zheng , Novielli Pierfrancesco , Romano Donato , Pantaleo Ester , Amoroso Nicola , Monaco Alfonso , Vacca Mirco , De Angelis Maria , Bellotti Roberto , Tangaro Sabina , Kuntzleman Abigail , Bigcraft Isaac , Techtmann Stephen , Bae Daehun , Kim Eunyoung , Jeon Jongbum , Joe Soobok ,   The Preterm Birth DREAM Community, Theis Kevin R. , Ng Sherrianne , Lee Li Yun S. , Diaz-Gimeno Patricia , Bennett Phillip R. , MacIntyre David A. , Stolovitzky Gustavo , Lynch Susan V. , Albrecht Jake , Gomez-Lopez Nardhy , Romero Roberto , Stevenson David K. , Aghaeepour Nima , Tarca Adi L. , Costello James C. , Sirota Marina
Published: March 2023

Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from raw sequences via an open-source tool, MaLiAmPi. We validated the crowdsourced models on novel datasets representing 331 samples from 148 pregnant individuals. From 318 DREAM challenge participants we received 148 and 121 submissions for our two separate prediction sub-challenges with top-ranking submissions achieving bootstrapped AUROC scores of 0.69 and 0.87, respectively. Alpha diversity, VALENCIA community state types, and composition (via phylotype relative abundance) were important features in the top performing models, most of which were tree based methods. This work serves as the foundation for subsequent efforts to translate predictive tests into clinical practice, and to better understand and prevent preterm birth.
Robustness Analysis of Colorectal Cancer Colonoscopy Screening Strategies
Authors: Nascimento de Lima Pedro , Rutter Carolyn M. , Maerzluft Christopher , Ozik Jonathan , Collier Nicholson
Published: March 2023

Colorectal Cancer (CRC) is a leading cause of cancer deaths in the United States. Despite significant overall declines in CRC incidence and mortality, there has been an alarming increase in CRC among people younger than 50. This study uses an established microsimulation model, CRC-SPIN, to perform a ‘stress test’ of colonoscopy screening strategies. First, we expand CRC-SPIN to include birth-cohort effects. Second, we estimate natural history model parameters via Incremental Mixture Approximate Bayesian Computation (IMABC) for two model versions to characterize uncertainty while accounting for increased early CRC onset. Third, we simulate 26 colonoscopy screening strategies across the posterior distribution of estimated model parameters, assuming four different colonoscopy sensitivities (104 total scenarios). We find that model projections of screening benefit are highly dependent on natural history and test sensitivity assumptions, but in this stress test, the policy recommendations are robust to the uncertainties considered.
Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus
Authors: Iannitelli Alexa F. , Hassenein Leslie , Mulvey Bernard , Blankenship Harris E. , Liles L. Cameron , Sharpe Amanda L. , Pare Jean-Francoise , Segal Arielle , Sloan Steven A. , Martinowich Keri , McCann Katharine E. , Dougherty Joseph D. , Smith Yoland , Beckstead Michael J. , Weinshenker David
Published: March 2023

The locus coeruleus (LC), the major source of norepinephrine (NE) in the brain, is an early site of pathology in both Alzheimer’s disease (AD) and Parkinson’s disease (PD), and it undergoes catastrophic degeneration later in both disorders. Dysregulation of the LC is thought to contribute to prodromal symptoms of AD and PD such as anxiety and sleep disturbances, while frank LC-NE loss promotes cognitive decline. However, the mechanisms responsible for its selective vulnerability are unknown. The LC is among the only structures in the brain that produces appreciable amounts of neuromelanin (NM), a dark cytoplasmic pigment. It has been proposed that NM initially plays a protective role by sequestering toxic catecholamine metabolites and heavy metals, but may become harmful during aging as it overwhelms cellular machinery and is released during neurodegeneration. Rodents do not naturally produce NM, limiting the study of causal relationships between NM and LC pathology. Adapting a viral-mediated approach for expression of human tyrosinase, the enzyme responsible for peripheral melanin production, we successfully promoted pigmentation in mouse LC neurons that recapitulates key ultrastructural features of endogenous NM found in primates. Pigment expression results in LC neuron hyperactivity, reduced tissue NE levels, transcriptional changes, and novelty-induced anxiety phenotypes as early as 1-week post-injection. By 6-10 weeks, NM accumulation is associated with severe LC neuron neurodegeneration and microglial engulfment of the pigment granules, while the anxiety-like behavior is abated. These phenotypes are reminiscent of LC dysfunction and cell death in AD and PD, validating this model for studying the consequences of pigment accumulation in the LC as it relates to neurodegenerative disease.
Synthetic Mucus Biomaterials for Antimicrobial Peptide Delivery
Authors: Yang Sydney , Duncan Gregg
Published: March 2023

Despite the promise of antimicrobial peptides (AMPs) as treatments for antibiotic-resistant infections, their therapeutic efficacy is limited due to the rapid degradation and low bioavailability of AMPs. To address this, we have developed and characterized a synthetic mucus (SM) biomaterial capable of delivering AMPs and enhancing their therapeutic effect. LL37 loaded SM hydrogels demonstrated controlled release of LL37 over 8 hours as a result of charge-mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 hours, LL37-SM hydrogels inhibitedPseudomonas aeruginosaPAO1 growth over 12 hours. LL37-SM hydrogel treatment reduced PAO1 viability over 6 hours whereas a rebound in bacterial growth was observed when treated with LL37 only. These data demonstrate LL37-SM hydrogels enhance antimicrobial activity by preserving LL37 AMP activity and bioavailability. Overall, this work establishes SM biomaterials as a platform for enhanced AMP delivery for antimicrobial applications.
The Sense of Body Ownership and the Neural Processes of Memory Encoding and Reinstatement
Authors: Iriye H. , Chancel M. , Ehrsson H. H.
Published: March 2023

Every event we experience that results in a memory involves experiencing our conscious self at its heart. The spatial and perceptual experience of one’s own body is the most basic form of selfhood. Disrupting bodily selfhood during memory formation impairs functioning of the hippocampus during retrieval, which implies a weakening of encoding mechanisms. However, neural activity present as individuals encode memories during manipulations of bodily selfhood have yet to be assessed. We investigated how body ownership, a core aspect of bodily selfhood, impacts encoding processes in the hippocampus and additional core memory regions (e.g. posterior parietal cortex). Further, we assessed the degree to which memories are reinstated according to body ownership during encoding and vividness during retrieval as a measure of memory strength. Participants viewed immersive videos through VR glasses, which depicted everyday events that included a first-person view of a mannequin’s body aligned with participants’ real bodies during fMRI scanning. We manipulated feelings of body ownership over the mannequin using a perceptual full-body illusion. One week later, participants retrieved memories for the videos during fMRI scanning. We observed that patterns of activity in several regions including the hippocampus and posterior parietal cortex distinguished between videos encoded with strong versus weak illusory body ownership. Moreover, these same regions reinstated memories to a greater degree when they were formed with a strong sense of body ownership and retrieved with increasing levels of vividness. Our findings demonstrate how the fundamental sense of owning one’s body shape neural signatures of memory formation and strengthen reinstatement at retrieval.
Similar structural area modulates local inhibition initiating post-lesion adaptive mechanism
Authors: Chakraborty Priyanka , Saha Suman , Deco Gustavo , Banerjee Arpan , Roy Dipanjan
Published: March 2023

The focal lesion, a form of biological perturbation damaging anatomical architecture, reasonably alters the normative healthy functional pattern but may recover over time. Nevertheless, how the brain counters deterioration in structure by global reshaping of functional connectivity (FC) after a lesion is largely unknown. We propose a novel equivalence principle based on structural and dynamic similarity analysis to predict specific compensatory areas initiating lost excitatory-inhibitory (E-I) regulation after lesion. We hypothesize that similar structural areas (SSAs) and dynamically similar areas (DSAs) corresponding to a lesioned site are the crucial dynamical units to restore lost homeostatic balance within the surviving cortical brain regions. SSAs and DSAs are independent measures, one based on structural similarity properties measured by Jaccard Index and the other based on post-lesion recovery time. Thereafter, a large-scale mean field model is deployed on top of a virtually lesioned structural connectome for characterizing the global brain dynamics and functional connectivity at the level of individual subjects. Despite inter-individual variability in SSAs, we found a general normative pattern in functional re-organization within the ipsi- and contra-lesional regions. The study demonstrates how SSAs and DSAs largely predict overlapping brain regions for different lesion centers/sites irrespective of the complexity of the lesion recovery process. The proposed computational framework captures the improvement of large-scale cortical cohesion by re-adjusting local inhibition. Our results further suggest that the predicted brain areas participating in recovery are not randomly distributed and widespread over the brain. Instead, the predicted brain areas are predominantly recruited from the ipsilesional hemisphere, barring a few regions from contra, suggesting that wiring proximity and similarity are the two major guiding principles of compensation-related utilization of hemisphere (CRUH) in the post-lesion FC re-organization process. Our finding further suggests that the re-organization of FC arises from the interplay between the underlying structural connectivity profile and the local inhibitory weights influencing compensatory coordinated brain dynamics during post-lesion recovery.
Dynamic network-guided CRISPRi screen reveals CTCF loop-constrained nonlinear enhancer-gene regulatory activity in cell state transitions
Authors: Luo Renhe , Yan Jielin , Oh Jin Woo , Xi Wang , Shigaki Dustin , Wong Wilfred , Cho Hyunwoo , Murphy Dylan , Cutler Ronald , Rosen Bess P. , Pulecio Julian , Yang Dapeng , Glenn Rachel , Chen Tingxu , Li Qing V. , Vierbuchen Thomas , Sidoli Simone , Apostolou Effie , Huangfu Danwei , Beer Michael A.
Published: March 2023

Comprehensive enhancer discovery is challenging because most enhancers, especially those affected in complex diseases, have weak effects on gene expression. Our network modeling revealed that nonlinear enhancer-gene regulation during cell state transitions can be leveraged to improve the sensitivity of enhancer discovery. Utilizing hESC definitive endoderm differentiation as a dynamic transition system, we conducted a mid-transition CRISPRi-based enhancer screen. The screen discovered a comprehensive set of enhancers (4 to 9 per locus) for each of the core endoderm lineage-specifying transcription factors, and many enhancers had strong effects mid-transition but weak effects post-transition. Through integrating enhancer activity measurements and three-dimensional enhancer-promoter interaction information, we were able to develop a CTCF loop-constrained Interaction Activity (CIA) model that can better predict functional enhancers compared to models that rely on Hi-C-based enhancer-promoter contact frequency. Our study provides generalizable strategies for sensitive and more comprehensive enhancer discovery in both normal and pathological cell state transitions.
Pectin methylesterification modulates cell wall properties to promote neighbour proximity-induced hypocotyl growth
Authors: Sénéchal Fabien , Robinson Sarah , Van Schaik Evert , Trévisan Martine , Saxena Prashant , Reinhardt Didier , Fankhauser Christian
Published: March 2023

Plants growing with neighbours compete for light and consequently increase growth of their vegetative organs to enhance access to sunlight. This response, called shade avoidance syndrome (SAS), involves photoreceptors such as phytochromes as well as phytochrome interacting factors (PIFs), which regulate the expression of growth-mediating genes. Numerous cell wall-related genes belong to the putative targets of PIFs, and the importance of cell wall modifications for enabling growth was extensively shown in developmental models such as dark-grown hypocotyl. However, the role of the cell wall in the growth of de-etiolated seedlings regulated by shade cues remains poorly established. Through analyses of mechanical and biochemical properties of the cell wall coupled with transcriptomic analysis of cell wall-related genes, we show the importance of cell wall modifications in neighbour proximity-induced elongation. Further analysis using loss-of-function mutants impaired in the synthesis and remodeling of the main cell wall polymers corroborated this. We focused on thecgr2cgr3double mutant that is defective in homogalacturonan (HG) methyltransferase activity required for methylesterification of HG-type pectins. By following hypocotyl growth kinetically and spatially and analyzing the mechanical and biochemical properties of cell walls, we found that methylesterification of HG-type pectins was required to enable global cell wall modifications. Moreover, HG-class pectin modification was needed for plant competition-induced hypocotyl growth. Collectively our work suggests that in the hypocotyl PIFs orchestrate changes in the expression of numerous cell wall genes to enable neighbour proximity-induced growth.

One sentence summary

The degree of methylesterification of pectins modulates global changes in the cell wall and its mechanical properties that contribute to the neighbour proximity-induced hypocotyl growth in Arabidopsis
Assessing the utility of COVID-19 case reports as a leading indicator for hospitalization forecasting in the United States
Authors: Reich Nicholas G , Wang Yijin , Burns Meagan , Ergas Rosa , Cramer Estee Y , Ray Evan L
Published: March 2023

Identifying data streams that can consistently improve the accuracy of epidemiological forecasting models is challenging. Using models designed to predict daily state-level hospital admissions due to COVID-19 in California and Massachusetts, we investigated whether incorporating COVID-19 case data systematically improved forecast accuracy. Additionally, we considered whether using case data aggregated by date of test or by date of report from a surveillance system made a difference to the forecast accuracy. Evaluating forecast accuracy in a test period, after first having selected the best-performing methods in a validation period, we found that overall the difference in accuracy between approaches was small, especially at forecast horizons of less than two weeks. However, forecasts from models using cases aggregated by test date showed lower accuracy at longer horizons and at key moments in the pandemic, such as the peak of the Omicron wave in January 2022. Overall, these results highlight the challenge of finding a modeling approach that can generate accurate forecasts of outbreak trends both during periods of relative stability and during periods that show rapid growth or decay of transmission rates. While COVID-19 case counts seem to be a natural choice to help predict COVID-19 hospitalizations, in practice any benefits we observed were small and inconsistent.
“Creating a culturally competent pharmacy profession”: a qualitative exploration of pharmacy staff perspectives of cultural competence and its training in community pharmacy settings
Authors: McCann Jessica , Lau Wing Man , Husband Andy , Todd Adam , Sile Laura , Doll Amandeep Kaur , Varia Sneha , Robinson-Barella Anna
Published: March 2023

Introduction

Cultural competence is an important attribute underpinning interactions between healthcare professionals, such as pharmacists, and patients from ethnic minority communities. Health- and medicines-related inequalities affecting people from underrepresented ethnic groups, such as poorer access to healthcare services and poorer overall treatment outcomes in comparison to their White counterparts, have been widely discussed in existing literature. Community pharmacies are a first port of call healthcare service accessed by diverse patient populations; yet, limited research exists which explores the perceptions of culturally competent care within the profession, or the delivery of cultural competence training to community pharmacy staff. This research seeks to gather perspectives of community pharmacy teams relating to cultural competence and identify possible approaches for the adoption of cultural competence training.

Methods

Semi-structured interviews were conducted in-person, over the telephone orviavideo call, between October-December 2022. Perspectives on cultural competence and training were discussed. Interviews were audio-recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the [anonymised] University Ethics Committee (ref: 25680/2022).

Results

Fourteen participants working in community pharmacies were interviewed, including: 8 qualified pharmacists, 1 foundation trainee pharmacist, 3 pharmacy technicians/dispensers and 2 counter assistants. Three themes were developed from the data which centred on: (1) defining and appreciating cultural competency within pharmacy services; (2) identifying pharmacies as “cultural hubs” for members of the diverse, local community; and (3) delivering cultural competence training for the pharmacy profession.

Conclusion

The results of this study offer new insights and suggestions on the delivery of cultural competence training to community pharmacy staff, students and trainees entering the profession. Collaborative co-design approaches between patients and pharmacy staff could enable improved design, implementation and delivery of culturally competent pharmacy services.

Patient or public contribution

The Patient and Public Involvement and Engagement group at [anonymised] University had input in the study design and conceptualisation. Two patient champions inputted to ensure that the study was conducted, and the findings were reported, with cultural sensitivity.

Trial registration

Not applicable. Ethical approval was obtained from the [anonymised] University Research and Ethics Committee (reference: 25680/2022).
HadzaPrevotellaRequire Diet-derived Microbiota Accessible Carbohydrates to Persist in Mice
Authors: Gellman Rebecca H , Olm Matthew R , Terrapon Nicolas , Enam Fatima , Higginbottom Steven K , Sonnenburg Justin L , Sonnenburg Erica D
Published: March 2023

Industrialization has transformed the gut microbiota, reducing the prevalence ofPrevotellarelative toBacteroides. Here, we isolateBacteroidesandPrevotellastrains from the microbiota of Hadza hunter-gatherers of Tanzania, a population with high levels ofPrevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence ofPrevotella copribut notBacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, andin vitrogrowth reveal that HadzaPrevotellastrains specialize in degrading plant carbohydrates, while HadzaBacteroidesisolates use both plant and host-derived carbohydrates, a difference mirrored inBacteroidesfrom non-Hadza populations. When competing directly,P. coprirequires plant-derived MACs to maintain colonization in the presence ofB. thetaiotaomicron, as a no MAC diet eliminatesP. copricolonization.Prevotella’sreliance on plant-derived MACs andBacteroides’ability to use host mucus carbohydrates could explain the reduced prevalence ofPrevotellain populations consuming a low-MAC, industrialized diet.

Statement on work with indigenous communities

In order to acquire scientific knowledge that accurately represents all human populations, rather than only reflecting and benefiting those in industrialized nations, it is necessary to involve indigenous populations in research in a legal, ethical, and non-exploitative manner (Abdill et al., 2022; Green et al., 2020). Here, we isolated live bacterial strains from anonymized fecal samples collected from Hadza hunter-gatherers in 2013/2014 (Fragiadakis et al., 2019; Merrill et al., 2022; Smits et al., 2017). Samples were collected with permission from the Tanzanian government, National Institute of Medical Research (MR/53i 100/83, NIMR/HQ/R.8a/Vol.IX/1542), the Tanzania Commission for Science and Technology, and with aid from Tanzanian scientists. A material transfer agreement with the National Institute for Medical Research in Tanzania specifies that collected samples are solely to be used for academic purposes. For more information on the consent practices followed, and our ongoing work to communicate the results of these projects to the Hadza, please see (Merrill et al., 2022; Olm et al., 2022).
Altered brain energy metabolism related to astrocytes in Alzheimer’s disease
Authors: Hirata Kosei , Matsuoka Kiwamu , Tagai Kenji , Endo Hironobu , Tatebe Harutsugu , Ono Maiko , Kokubo Naomi , Oyama Asaka , Shinotoh Hitoshi , Takahata Keisuke , Obata Takayuki , Dehghani Masoumeh , Near Jamie , Kawamura Kazunori , Zhang Ming-Rong , Shimada Hitoshi , Yokota Takanori , Tokuda Takahiko , Higuchi Makoto , Takado Yuhei
Published: March 2023

Objective

Increasing evidence suggests that reactive astrocytes are associated with Alzheimer’s disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered energy metabolism. It is hypothesized that lactate, a glucose metabolite, is produced in astrocytes and subsequently shuttled to neurons as an energy substrate. This study aimed to examine alterations in brain lactate levels and their association with astrocytic activities in AD.

Methods

30 AD and 30 cognitively unimpaired (CU) subjects were enrolled. For AD subjects, amyloid and tau depositions were confirmed by positron emission tomography using [11C]PiB and [18F]florzolotau, respectively. Lactate and myo-inositol, an astroglial marker, in the posterior cingulate cortex (PCC) were quantified by magnetic resonance spectroscopy (MRS). These MRS metabolites were compared with plasma biomarkers, including glial fibrillary acidic protein (GFAP) as another astrocytic marker.

Results

Lactate and myo-inositol levels were higher in AD than in CU (p< 0.05). Lactate levels correlated with myo-inositol levels (r= 0.272,p= 0.047). Lactate and myo-inositol levels were positively associated with the Clinical Dementia Rating sum-of-boxes scores (p< 0.05). Significant correlations were noted between myo-inositol levels and plasma GFAP and tau phosphorylated at threonine 181 levels (p< 0.05).

Interpretation

We found high lactate levels accompanied by an increased astrocytic marker in the PCC in AD. Thus, impaired lactate shuttle of reactive astrocytes may disrupt energy regulation, resulting in surplus lactate levels. Myo-inositol and plasma GFAP may reflect similar astrocytic changes.
Knowledge and awareness of Pre-exposure Prophylaxis among men in sub-Saharan Africa: A scoping review protocol
Authors: Badru Oluwaseun Abdulganiyu , Hlongwa Mbuzeleni , Adeagbo Oluwafemi Atanda
Published: March 2023

Introduction

About 38.4 million people were living with HIV as of 2021, and HIV is more prevalent in sub-Saharan Africa. Pre-exposure prophylaxis (PrEP) is highly effective in HIV prevention. Despite the efficacy of PrEP, many persons, including men, do not have adequate knowledge and awareness of PrEP, and reviews on knowledge and awareness among men are scarce. This review aims to assess and synthesize the knowledge and awareness of PrEP among persons assigned as males at birth in sub-Saharan Africa.

Method and analysis

The proposed scoping review will be conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. The following information sources will be searched to retrieve relevant studies for this review: CINAHL, MEDLINE (Ovid), PubMed, SCOPUS, and Web of Science. Google Scholar, The Union Catalogue of Theses and Dissertations (UCTD) and SA ePublications via SABINET Online, WorldCat Dissertations and Theses via OCLC, ResearchGate, and American Doctoral Dissertations via EBSCOhost. All study designs, except existing reviews, will be included. All screenings (abstract screening and full-text screening) and data extraction will be conducted independently by two reviewers. Quantitative findings will be presented with frequency and percentages, while qualitative thematic analysis will be used to analyze qualitative findings.

Ethics and dissemination

Due to the use of primary published data, ethical approval is not required for this review. The results of this review will be presented at a conference and published in a high-impact peer-review journal.
A systematic review of the effectiveness and implementation readiness of psychosocial interventions for psychosis in South Asia
Authors: Lyles Sophie , Khan Zahra , Qureshi Onaiza , Shaikh Madiha
Published: March 2023

Background

Little is known about the effectiveness and implementation of psychosocial interventions for psychosis in low- and middle-income countries (LMICs). In South Asia, specialist psychiatric resources are scarce. Support for psychosis often falls on the family or caregiver which can increase feelings of burden, impact caregivers’ wellbeing, and increase mental health stigma. Psychosocial interventions are increasingly used for psychosis in South Asia and could reduce relapse and symptoms, reduce caregiver burden, conserve cost and resources. The aim of this review was to appraise the effectiveness and implementation readiness of psychosocial interventions for people with psychosis in LMICs within South Asia.

Method

A systematic search was conducted on MEDLINE, PsycINFO, Global Health, and Web of Science. The review was prospectively registered on PROSPERO (CRD42022329254). Studies were rated on two scales assessing quality and implementation readiness.

Results

Twenty-six papers were included, nine intervention-types including community-based interventions/assertive outreach; CaCBTp; FAP; psychoeducation; cognitive retraining/rehabilitation; social cognition/skills; family/ caregiver intervention; telehealth intervention; yoga-based intervention in six South Asian countries.

Findings suggest a multicomponent community-based intervention (MCBI) was the most implementation ready due to its standardisation, good clinical outcome outcomes for patients and caregivers, and training and cost evaluations.

Conclusion

Of the included studies, MCBI and community-based outreach interventions utilising lay health workers appear to be the most implementation ready and are suggested to best address the treatment gap in South Asia.
Performance of urinary phenyl-γ-valerolactones as biomarkers of dietary flavan-3-ol exposure
Authors: Parmenter Benjamin H. , Shinde Sujata , Croft Kevin , Murray Kevin , Bondonno Catherine P. , Genoni Angela , Christophersen Claus T. , Biden Keren , Kay Colin , Mena Pedro , Del Rio Daniele , Hodgson Jonathan M. , Bondonno Nicola P.
Published: March 2023

Background

Phenyl-γ-valerolactones (PVLs) have been proposed as potential biomarkers of dietary flavan-3-ol exposure.

Objective

We investigate the performance of a range of PVLs as biomarkers indicative of flavan-3-ol intake.

Methods

We report results of two companion studies: a 5-way randomised cross-over trial (RCT) and an observational cross-sectional study. In the RCT, 16 healthy participants were randomly assigned to 1-day flavan-3-ol rich interventions (of either apple, cocoa, black tea, green tea, or water [control]). Participants collected 24-hour urine and first morning urine samples, with diet standardised throughout. For each participant, one of the five intervention periods was randomly extended to two days, to monitor PVL kinetics following repeated days of flavan-3-ol exposure. In the cross-sectional study, 86 healthy participants collected 24-hour urines and concurrent weighed food diaries from which flavan-3-ol consumption was estimated using Phenol-Explorer. A panel of 10 urinary PVLs was quantified using liquid chromatography tandem mass spectrometry.

Results

In both studies, two urinary PVLs [5-(3’ s-hydroxyphenyl)-γ-valerolactone-4’-sulfate and tentatively identified 5-(4’-hydroxyphenyl)-γ-valerolactone-3’-glucuronide] were the principal compounds excreted (>75%). In the RCT, the sum of these PVLs was significantly higher than the water (control) following each intervention; individually, there was a shift from sulfation towards glucuronidation as the total excretion of PVLs increased across the different interventions. In the extended RCT intervention period, after two days of treatment, there was no evidence of accumulation of these compounds in the urine, and following withdrawal of treatment on the third day, there was a return towards negligible PVL excretion. All results were consistent, whether compounds were measured in 24-hour urine or first morning voids. In the observational study, the sum of the principal PVLs correlated dose-dependently (Rs= 0.37,P= 0.0006) with dietary flavan-3-ol intake, with similar associations for each individually.

Conclusion

Urinary 5-(3’-hydroxyphenyl)-γ-valerolactone-4’-sulfate and tentatively identified 5-(4’-hydroxyphenyl)-γ-valerolactone-3’-glucuronide are recommended biomarkers for dietary flavan-3-ol exposure.
NN50 and pNN50, two time-domain heart rate variability parameters were associated with 30-day all-cause mortality in patients admitted to intensive care unit: A Retrospective Study of the MIMIC-IV Database
Authors: Li Sheran , Yang Qiyu , Wu Peiyu , Lu Yujing , Yang Zhengfei , Jiang Longyuan
Published: March 2023

Objective

Our study aims to evaluate the association between heart rate variability (HRV) and short and long-term prognosis in patients admitted to intensive care unit (ICU).

Methods and Results

Adult patients continuously monitored for over 24h in ICUs from the MIMIC-IV Waveform Database were recruited in our study. Twenty HRV-related variables (8 time-domain, 6 frequency-domain; and 6 nonlinear variables) were calculated based on RR intervals. The association between HRV and 30-day all-cause mortality was assessed. Ninety-three patients met the inclusion criteria and were classified into 30-day survivor group and non-survivor groups based on their survival status. The 30-day all-cause mortality rate was 17.2%. NN50 and pNN50 were both significantly higher in non-survivors compared to survivors, whereas the rest of the time-domain, frequency domain and non-linear HRV parameters did not differ significantly between the two groups (allP>0.05). In addition, at 180 days after admission, non-survivors had significantly higher levels of NN50 and rMSSD than the survivors. However, NN50 was not an independent predictor of 30-day all-cause mortality in patients by multivariate COX regression analysis (HR, 1.0; 95% CI, 1.000 - 1.001;P=0.594). The Area Under the Curve (AUC), cut-off value, sensitivity and specificity of NN50 for predicting 30-day all-cause mortality using ROC were 0.67, 799, 0.813 and 0.584, respectively. Plotting Kaplan-Meier analysis using this cut-off value showed that patients with high NN50 had considerably greater 30-day all-cause mortality than those with low NN50 (P< 0.001).

Conclusion

NN50 and pNN50 are associated with elevated 30-day all-cause mortality in ICU patients but are not independent predictors of all-cause mortality using multivariate COX regression analysis.
DEK oncoprotein participates in heterochromatin replication via SUMO-dependent nuclear bodies
Authors: Pierzynska-Mach Agnieszka , Czada Christina , Vogel Christopher , Gwosch Eva , Osswald Xenia , Bartoschek Denis , Diaspro Alberto , Kappes Ferdinand , Ferrando-May Elisa
Published: March 2023

The correct inheritance of chromatin structure is key for maintaining genome function and preventing cellular transformation. DEK, a conserved chromatin protein, has recognized tumor-promoting properties, its overexpression being associated with poor prognosis in various cancer types. At the cellular level, DEK displays pleiotropic functions, influencing differentiation, apoptosis, and stemness, but a characteristic oncogenic mechanism remains elusive. Here, we report the identification of DEK bodies, focal assemblies of DEK occurring at specific, yet unidentified sites of heterochromatin replication. In these bodies, DEK localizes in direct proximity to active replisomes suggesting a function in the early maturation of heterochromatin. A high-throughput siRNA screen identifies SUMO as a major regulator of DEK body formation, linking DEK to the SUMO network that controls chromatin states and cell fate. This work combines and refines our previous data on DEK as a factor essential for heterochromatin integrity and facilitating replication under stress and delineates an avenue of further study for unraveling DEK’s contribution to cancer development.
Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling
Authors: Danhof Heather A. , Lee Jihwan , Thapa Aanchal , Britton Robert A. , Di Rienzi Sara C.
Published: March 2023

Intestinal microbes impact the health of the intestine and organs distal to the gut.Limosilactobacillus reuteriis a human intestinal microbe that promotes normal gut transit1, the anti-inflammatory immune system2–4, wound healing5–7, normal social behavior in mice8–10, and prevents bone reabsorption11–17. Each of these functions is impacted by oxytocin18–22, and oxytocin signaling is required forL. reuteri-mediated wound healing5and social behavior9; however, the initiating events in the gut that lead to oxytocin stimulation and related beneficial functions remain unknown. Here we found evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, human intestinal organoids produce oxytocin, demonstrating that the intestinal epithelium is sufficient to produce oxytocin. We subsequently found thatL. reuterifacilitates oxytocin secretion directly from human intestinal tissue and human intestinal organoids. Finally, we demonstrate that stimulation of oxytocin secretion byL. reuteriis dependent on the gut hormone secretin, which is produced in enteroendocrine cells23, while oxytocin itself is produced in enterocytes. Altogether, this work demonstrates that oxytocin is produced and secreted from enterocytes in the intestinal epithelium in response to secretin stimulated byL. reuteri. This work thereby identifies oxytocin as an intestinal hormone and provides mechanistic insight into avenues by which gut microbes promote host health.
An Acoustically Controlled Microrobot Modelled onSpirocheteBacteria
Authors: Deng Yong , Paskert Adrian , Zhang Zhiyuan , Wittkowski Raphael , Ahmed Daniel
Published: March 2023

As a next-generation toolkit, microrobots can transform a wide range of fields, including micromanufacturing, electronics, microfluidics, tissue engineering, and medicine. While still in their infancy, acoustically actuated wireless microrobots are becoming increasingly attractive, as acoustic control can generate large propulsive forces, requires relatively simple microrobot design, and does not entail complex manipulation systems. However, the interaction of acoustics with microstructure geometry is poorly understood to date, and its study is necessary for developing next-generation acoustically powered microrobots. We present here a mass-manufactured acoustically driven helical microrobot capable of locomotion using a fin-like double-helix microstructure. This microrobot responds to sound stimuli and mimics the spiral motion of natural microswimmers such as spirochetes. The asymmetric double helix interacts with the incident acoustic field, inducing a propulsion torque that causes the microrobot to rotate around its long axis. Moreover, our microrobot has the unique feature of its directionality being switchable by simply tuning the acoustic frequency. We demonstrate this locomotion in 2D and 3D artificial vasculatures using a single sound source. Since ultrasound is widely used as an imaging modality in clinical settings, our robotic system can integrate seamlessly into practice; thus, our findings could contribute to the development of next-generation smart microrobots.

One-Sentence Summary

We present an acoustically driven helical microrobot capable of corkscrew-like locomotion using a double-helix microstructure.
A nanobody-based strategy for rapid and scalable purification of native human protein complexes
Authors: Stevens Taylor Anthony , Tomaleri Giovani Pinton , Hazu Masami , Wei Sophia , Nguyen Vy N. , DeKalb Charlene , Voorhees Rebecca M. , Pleiner Tino
Published: March 2023

Native isolation of proteins in high yield and purity is a major bottleneck for analysis of their three- dimensional structure, function, and interactome. Here, we present a streamlined workflow for the rapid production of proteins or protein complexes using lentiviral transduction of human suspension cells, combined with highly-specific nanobody-mediated purification and proteolytic elution. (1) First, generation of a plasmid coding for a protein of interest fused to an N- or C- terminal GFP or ALFA peptide tag is rapidly achieved using the lentiviral plasmid toolkit we have designed. (2) Human suspension cell lines stably expressing the tagged fusion protein can be generated in <5 days using lentiviral transduction. (3) Leveraging the picomolar affinity of the GFP and ALFA nanobodies for their respective tags, proteins expressed even at low levels can be specifically captured from the resulting cell lysate in a variety of conditions, including detergents and mild denaturants. (4) Finally, rapid and specific elution of tagged or untagged proteins under native conditions is achieved within minutes at 4°C using an engineered SUMO protease. We demonstrate the wide applicability of the method by purifying multiple challenging soluble and membrane protein complexes to high purity from human cells. Our strategy is also directly compatible with many widely used GFP expression plasmids, cell lines and transgenic model organisms; is faster than alternative approaches, requiring ∼8 days from cloning to purification; and results in substantially improved yields and purity.
Beware of the watchdog! Role communication in job advertisements for management accountants
Authors: Rieg Robert , Meier Jan-Hendrik , Finckh Carmen
Published: March 2023

Purpose

Job advertisements are important means of communicating role expectations for management accountants to the labor market. They provide information about which roles are sought and expected. However, which roles are communicated in job advertisements is unknown so far.

Design/methodology/approach

With a text-mining approach on a large sample of 889 job ads, the authors extract information on roles, type of firm and hierarchical position of the management accountant sought.

Findings

The results indicate an apparent mix of different role types with a strong focus on a classic watchdog role. However, the business partner role is more often sought for leadership positions or in family businesses and small- and medium-sized enterprises (SME).

Research limitations/implications

The main limitation is the lack of an agreed-upon measurement instrument for roles in job offers. The study results imply that corporate practice is not as theory-driven as is postulated and communicated in the management accounting community. This indicates the existence of a research-practice gap and tensions between different actors in the management accounting field.

Practical implications

The results challenge the current role discussion of professional organizations for management accountants as business partners.

Originality/value

The authors contribute the first study, which explicitly analyzes the communication of roles in job offers for management accountants. It indicates a discrepancy between scholarly discussion on roles and management accountants' work from an employer's perspective.
Challenge and hindrance demands of doctoral education: conceptualization, scale development and validation
Authors: Acharya Vrinda , Rajendran Ambigai , Prabhu Nandan
Published: March 2023

Purpose

The present study develops, conceptualizes and validates a scale based on the transactional stress theory to assess the perceived challenge and hindrance demands of doctoral programs that impact doctoral students’ psychological well-being.

Design/methodology/approach

This research employs an exploratory-mixed methodology comprising five phases with a sequential qualitative-quantitative approach. A rigorous scale development process is adopted to validate the instrument’s psychometric properties. The study respondents are Indian full-time doctoral students in the management discipline.

Findings

The findings show that the construct of perceived challenge and hindrance demands is a first-order four-factor and a second-order two-factor model. The study has validated the scale to capture the challenge and hindrance demands of doctoral research programs with the following sub-constructs: doctoral program resource inadequacies, doctoral program ambiguity, doctoral program workload and complexity.

Practical implications

The recommended challenge demands and hindrance demands (CHD) scale provides a benchmark for doctoral institutes and program supervisors in focussing on research students’ perception of their doctoral education demands to reduce the strain and increase their well-being during their doctoral program journey.

Originality/value

Hindrance demands adversely influence the motivation resources needed for doctoral education; challenge demands positively impact the research students’ internal resources.
The effect of cause-related marketing on the green consumption attitude–behaviour gap in the cosmetics industry
Authors: Venciute Dominyka , Kazukauskaite Migle , Correia Ricardo Fontes , Kuslys Marius , Vaiciukynas Evaldas
Published: March 2023

Purpose

The aim of the article is to analyze the effect of cause-related marketing on the attitude–behaviour gap of green consumption in the cosmetics industry. Specifically, the authors examine the relationship between attitude towards the environment, attitude towards green consumption, subjective norms of green consumption, green consumption intention, green consumption behaviour and cause-related marketing.

Design/methodology/approach

A cross-sectional research design was used to test the results of a random sample of 241 respondents and quantitative research was conducted using the data collected through an online questionnaire.

Findings

The research expanded the current knowledge on the effect of cause-related marketing on consumers’ green purchase behaviour and the findings suggested that green cosmetics producers and sellers should clearly define their target audience before choosing the type of cause-related marketing, as it mainly influences those consumers who have a positive attitude towards green consumption.

Research limitations/implications

The implications of the research are relevant for marketing specialists, managers and agencies who are looking to promote green cosmetics products.

Practical implications

Before promoting green cosmetics products, it is important to understand who the target consumer is and whether they have a positive attitude towards the environment, green consumption and also if they are affected by acquaintances’ opinions.

Originality/value

The study contributes to the already existing academic literature by providing a greater understanding of the effect of cause-related marketing on the attitude–behaviour gap of green consumption.