bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging protections, navigating punishments: How adult children of undocumented immigrants mediate illegality in Latinx families
Authors: Delgado Vanessa
Published: May 2022

Objective

The objective of this study is to examine how adult children of undocumented immigrants manage parental illegality in Latinx immigrant families.

Background

There are 16.7 million people who live with at least one undocumented family member in the U.S. today. Scholars have documented how children of undocumented immigrants can help navigate the negative consequences of illegality in their families. However, less is known about how the immigration status of these youth shapes the support they provide to their undocumented parents.

Method

This study draws on 41 in‐depth semi‐structured interviews with 19 DACAmented and 22 U.S.‐born citizen college students (18–27) who had at least one undocumented parent. Interviews were collected via snowball sampling technique at a large research university in Southern California.

Results

The findings suggest that citizen and DACAmented college students engage in distinct strategies when mediating illegality for their undocumented parents. Citizens attempt to leverage their protected legal status to help their undocumented parents become Lawful Permanent Residents and step in during situations where threats of deportation are imminent. DACAmented young adults draw on their experience with legal precarity to help their undocumented parents navigate punishments associated with their immigration status.

Conclusion

This research uncovers how parents' precarious legal status contributes to the intergenerational transmission of disadvantage among citizen and DACAmented young adults—and how these youths try to mediate the harms of illegality.

Implications

The strategies adult children of undocumented immigrants implement to negotiate illegality in their families highlights the need for policy addressing the legal vulnerability of undocumented and mixed status families.
Impact of rural hospital closures on hospitalizations and associated outcomes for ambulatory and emergency care sensitive conditions
Authors: Khushalani Jaya S. , Holmes Mark , Song Suhang , Arifkhanova Aziza , Randolph Randy , Thomas Sharita , Hall Diane M.
Published: May 2022

Purpose

The purpose of this paper is to examine the impact of rural hospital closures on age‐adjusted hospitalization rates for ambulatory care sensitive condition (ACSC) and emergency care sensitive condition (ECSC) and associated outcomes, such as length of stay and in‐hospital mortality in hospital service areas (HSAs) that utilized the closed hospital.

Methods

We used the State Inpatient Data from the Healthcare Cost and Utilization Project for 9 states from 2010 to 2017 and classified admissions as ACSC or ECSC. We compared age‐adjusted admission rates and length of stay (LOS) for ACSC and ECSC rates and age adjusted in‐hospital mortality rate for ECSC among rural ZIP codes in HSAs with a closure to rural ZIP codes in HSAs without closures. We used propensity score‐weighted regression analysis and event study design.

Findings

Findings suggest that ACSC admission rates started to increase right before the closure. However, this increase levels off 2 years after closure. LOS for ACSC significantly decreased almost a year after closure. ECSC admissions showed a significant decrease for a few quarters 1 year before the closure.

Conclusions

Rural hospital closures were associated with increase in ACSC admissions right before closure and for nearly 2 years post closure as well as decrease in ECSC admissions before closure. As rural hospitals continue to close, efforts to ensure communities affected by these closures maintain access to primary health care may help eliminate increases in costly preventable hospital admissions for ACSC while ensuring access for emergency care services.
GmTDN1 improves wheat yields by inducing dual tolerance to both drought and low‐N stress
Authors: Zhou Yongbin , Liu Jun , Guo Jinkao , Wang Yanxia , Ji Hutai , Chu Xiusheng , Xiao Kai , Qi Xueli , Hu Lin , Li Hui , Hu Mengyun , Tang Wensi , Yan Jiji , Yan Huishu , Bai Xinxuan , Ge Linhao , Lyu Mingjie , Chen Jun , Xu Zhaoshi , Chen Ming , Ma Youzhi
Published: May 2022

Genetically enhancing drought tolerance and nutrient use efficacy enables sustainable and stable wheat production in drought‐prone areas exposed to water shortages and low soil fertility, due to global warming and declining natural resources. In this study, wheat plants, exhibiting improved drought tolerance and N‐use efficacy, were developed by introducing GmTDN1, a gene encoding a DREB‐like transcription factor, into two modern winter wheat varieties, cv Shi4185 and Jimai22. Overexpressing GmTDN1 in wheat resulted in significantly improved drought and low‐N tolerance under drought and N‐deficient conditions in the greenhouse. Field trials conducted at three different locations over a period of 2–3 consecutive years showed that both Shi4185 and Jimai22 GmTDN1 transgenic lines were agronomically superior to wild‐type plants, and produced significantly higher yields under both drought and N‐deficient conditions. No yield penalties were observed in these transgenic lines under normal well irrigation conditions. Overexpressing GmTDN1 enhanced photosynthetic and osmotic adjustment capacity, antioxidant metabolism, and root mass of wheat plants, compared to those of wild‐type plants, by orchestrating the expression of a set of drought stress‐related genes as well as the nitrate transporter, NRT2.5. Furthermore, transgenic wheat with overexpressed NRT2.5 can improve drought tolerance and nitrogen (N) absorption, suggesting that improving N absorption in GmTDN1 transgenic wheat may contribute to drought tolerance. These findings may lead to the development of new methodologies with the capacity to simultaneously improve drought tolerance and N‐use efficacy in cereal crops to ensure sustainable agriculture and global food security.
Identification of a stripe rust resistance gene YrSF in Chinese wheat (Triticum aestivum) landrace Sifangmai
Authors: Feng Jing , Sun Jian Lu , Shah Syed Jawad Ahmad , Wang Fengtao , Yao Qiang , Guo Qingyun , Lin Ruiming , Xu Shichang
Published: May 2022

Wheat stripe rust is an important disease and can seriously threaten wheat production. The most economical, safe and effective approach to manage this disease is to breed and deploy resistant varieties. Sifangmai is a Chinese wheat landrace and maintained adequate resistance to the Chinese stripe rust races. In order to decipher genetic bases of resistance in Sifangmai, the F1, F2 and F2:3 of the cross Sifangmai/Taichung 29 were tested at adult stage with race CYR32. Genetic analysis revealed that resistance in Sifangmai was controlled by a single dominant gene named as YrSF. Six SSR on chromosome 5BS showed polymorphism among ‘Taichung 29’, Sifangmai, and resistant and susceptible bulks. Chinese Spring nulli‐tetrasomic and monosomic lines were confirmed YrSF on chromosome 5B. A linkage map of YrSF was constructed and the closely linked marker to YrSF was Xgpw8015 with 1.8 cM. Based on the comparisons of resistance infection type, pedigree analysis, gene origin and chromosomal position of previously reported Yr genes on chromosome 5B, YrSF is different from these known genes and is likely a novel gene.
Occupational COPD—The most under‐recognized occupational lung disease?
Authors: Murgia Nicola , Gambelunghe Angela
Published: May 2022

Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious particles and gases. Smoking is the main risk factor, but other factors are also associated with COPD. Occupational exposure to vapours, gases, dusts and fumes contributes to the development and progression of COPD, accounting for a population attributable fraction of 14%. Workplace pollutants, in particular inorganic dust, can initiate airway damage and inflammation, which are the hallmarks of COPD pathogenesis. Occupational COPD is still underdiagnosed, mainly due to the challenges of assessing the occupational component of the disease in clinical settings, especially if other risk factors are present. There is a need for specific education and training for clinicians, and research with a focus on evaluating the role of occupational exposure in causing COPD. Early diagnosis and identification of occupational causes is very important to prevent further decline in lung function and to reduce the health and socio‐economic burden of COPD. Establishing details of the occupational history by general practitioners or respiratory physicians could help to define the occupational burden of COPD for individual patients, providing the first useful interventions (smoking cessation, best therapeutic management, etc.). Once patients are diagnosed with occupational COPD, there is a wide international variation in access to specialist occupational medicine and public health services, along with limitations in workplace and income support. Therefore, a strong collaboration between primary care physicians, respiratory physicians and occupational medicine specialists is desirable to help manage COPD patients' health and social issues.
Sentence‐Final Particles in Mandarin*
Authors: Fang Hongmei , Hengeveld Kees
Published: May 2022

Mandarin Chinese is rich in sentence‐final particles, which have to follow a rigid linear order when they cluster. In much of the literature, researchers focus on clarifying the functions of individual particles, with less attention being paid to the explanations of their highly restricted order. Based on corpus data and using the framework of Functional Discourse Grammar (FDG, Hengeveld & Mackenzie 2008), this paper explores the questions which particles can cluster and why they cluster in a specific order. We show that maximally three Mandarin sentence‐final particles can cluster, and we argue that their sequence is restricted by their positioning in a strict four‐layered hierarchical structure, in which each particle pertains to a specific semantic or pragmatic layer. In addition, Mandarin particles provide evidence that there are operators at a higher discourse level than so far assumed to exist in FDG.
Expression of the hedgehog signalling pathway and the effect of inhibition at the level of smoothened in canine osteosarcoma cell lines
Authors: Nam Aryung , Song Woo‐Jin , An Ju‐Hyun , Rebhun Robert B. , Youn Hwa‐Young , Seo Kyoung‐Won
Published: May 2022

Osteosarcoma (OSA) is the most common malignant bone cancer in dogs. Canine and human OSA share several features, including tumour environments, response to traditional treatment, and several molecular pathways. Hedgehog (Hh) signalling is known to contribute to tumorigenesis and progression of various cancers, including human OSA. This study aimed to identify the role of the Hh signalling pathway in canine OSA cell lines, including Abrams, D17, and Moresco, focusing on the signal transducer Smoothened (SMO). mRNA and protein levels of Hh pathway components, including SHH, IHH, SMO, and PTCH1, were aberrant in all examined OSA cell lines compared with canine osteoblast cells. The SMO inhibitor cyclopamine significantly decreased cell viability and colony‐forming ability in the canine OSA cell lines in a dose‐dependent manner. Moresco cells, which expressed the highest level of SMO protein, were the most sensitive to the anticancer effect of cyclopamine among the three canine OSA cell lines tested. Hh downstream target gene and protein expression in canine OSA cell lines were downregulated after cyclopamine treatment. In addition, cyclopamine significantly increased apoptotic cell death in Abrams and Moresco cells. The findings that Hh/SMO is activated in canine OSA cell lines and cyclopamine suppresses OSA cell survival via inhibition of SMO suggest that the Hh/SMO signalling pathway might be a novel therapeutic target for canine OSA.
The effects of sex and neuter status on trauma survival in dogs: A Veterinary Committee on Trauma registry study
Authors: Fontes Gabrielle S. , McCarthy Robert J. , Kutzler Michelle A. , Zitek‐Morrison Emily
Published: May 2022

Objective

To determine the effect of sex and neuter status on trauma survival in dogs.

Design

Multi‐institutional prospective case series, September 2013 to March 2019, retrospectively analyzed.

Setting

Level I and II Veterinary Trauma Centers.

Animals

Consecutive sample of 2649 dogs in the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma patient registry meeting inclusion criteria. For inclusion, dogs had to have complete data entries, be postpubertal (≥7 months age in females and ≥10 months age in males), and have sustained moderate to severe trauma (animal trauma triage [ATT] score ≥5/18). Dogs that were dead upon arrival, euthanized for financial or unknown reasons alone, or that were presented by a Good Samaritan but subsequently humanely euthanized were excluded.

Measurements and Main Results

Data collected included age, sex, neuter status (intact, neutered), trauma type (blunt, penetrating, both), outcome (survived to hospital discharge, died, euthanized), and reason for euthanasia (grave prognosis, financial reasons, or both). Of 2649 eligible dogs, 56% survived to hospital discharge (n = 1469). Neutered females had a significantly higher survival rate (58.3% vs 51.3%; P = 0.03) compared to intact females, and neutered males had a significantly higher survival rate (56.6% vs 50.7%; P = 0.04) compared to intact males. There was no significant difference in survival between intact females and intact males (P = 0.87) or between neutered females and neutered males (P = 0.46). Mean cumulative ATT score was higher in intact groups and was found to be a significant predictor of survival (P < 0.01). Based on logistic models, overall odds of survival were 20.7% greater in neutered dogs.

Conclusions

Gonadectomy is associated with lower ATT scores and improved survival after moderate to severe trauma in both female and male dogs.
Fracaso de la paz y el desarme, desmovilización y reintegración (DDR)
Authors: Gonzalez Peña Andrea del Pilar
Published: May 2022

Los estudios existentes sugieren que los programas de DDR no fortalecen la paz después de las negociaciones. Esta investigación argumenta que los diversos componentes de DDR pueden tener diferentes impactos en el fracaso de la paz. Este documento examina las implicaciones de cada componente del proceso de DDR en una negociacion de paz para prevenir la recurrencia de la guerra. Esta investigación responde la siguiente pregunta: ¿una negociación de DDR, en las negociaciones de los conflictos armados, previene la recurrencia de la guerra en el escenario de postconflicto? Utilizando una base de datos original que registra 102 procesos de negociación de paz durante el período 1975 a 2012, demuestro que es más probable que se logre la paz cuando el acuerdo de paz incluye una disposición de DDR, especialmente el proceso de reintegración.
Bayesian design of broadband multilayered microperforated panel absorbers
Authors: Xiang Ning , Fackler Cameron J. , Hou Yiqiao , Schmitt Andrew A. J.
Published: May 2022

In some noise control and architectural acoustics applications, nonfibrous, hygienic materials are desirable or even strictly required. In meeting such restrictive requirements, microperforated panel (MPP) sound absorbers represent a potential solution. Yet, they typically possess limited absorption bandwidth. Combining multiple MPPs into a multilayer system may broaden the absorption frequency ranges while maintaining high absorption. When increasing the overall absorption bandwidth, each additional MPP layer also increases the complexity of the design process because the design parameters are correspondingly increased by four per each additional layer. This paper applies a Bayesian inferential framework to the design of multilayer MPP absorbers with a parsimonious structural configuration, which penalizes the overlayered configurations. This Bayesian framework demonstrates that the practical design of multilayer MPP absorbers may be accomplished with two levels of model-based inference: model selection and parameter estimation. The design process proceeds inversely from a design target to design parameters, including the required number of MPP layers and their corresponding MPP parameters. This paper discusses the Bayesian design formulation, unified implementation of two levels of Bayesian inference, and experimental validation of a Bayesian design for a multilayered MPP absorber, which is able to meet the design target arising from practice.
Output compensation of auditory brainstem responses in dolphins and sea lions
Authors: Finneran James J. , Mulsow Jason , Strahan Madelyn G. , Houser Dorian S. , Burkard Robert F.
Published: May 2022

Cochlear dispersion causes increasing delays between neural responses from high-frequency regions in the cochlear base and lower-frequency regions toward the apex. For broadband stimuli, this can lead to neural responses that are out-of-phase, decreasing the amplitude of farfield neural response measurements. In the present study, cochlear traveling-wave speed and effects of dispersion on farfield auditory brainstem responses (ABRs) were investigated by first deriving narrowband ABRs in bottlenose dolphins and California sea lions using the high-pass subtractive masking technique. Derived-band ABRs were then temporally aligned and summed to obtain the “stacked ABR” as a means of compensating for the effects of cochlear dispersion. For derived-band responses between 8 and 32 kHz, cochlear traveling-wave speeds were similar for sea lions and dolphins [∼2–8 octaves (oct)/ms for dolphins; ∼3.5–11 oct/ms for sea lions]; above 32 kHz, traveling-wave speed for dolphins increased up to ∼30 oct/ms. Stacked ABRs were larger than unmasked, broadband ABRs in both species. The amplitude enhancement was smaller in dolphins than in sea lions, and enhancement in both species appears to be less than reported in humans. Results suggest that compensating for cochlear dispersion will provide greater benefit for ABR measurements in species with better low-frequency hearing.
Automated detection of blue whale D-calls using deep learning with a double-observer performance assessment
Authors: Madhusudhana Shyam , Miller Brian S. , Aulich Meghan G. , Kelly Nat
Published: May 2022

An automated algorithm for passive acoustic detection of blue whale D-calls is developed based on established deep learning methods for image recognition via the DenseNet architecture. Koogu—an open-source Python package—was used for developing the detector. The detector was trained on annotated acoustic recordings from the Antarctic, and the performance of the detector was assessed by calculating precision and recall using a separate independent dataset also from the Antarctic. Detections from both the human analyst and automated detector were then inspected by a more experienced analyst to identify any calls missed by either approach and to adjudicate whether the apparent false-positive detections from the automated approach were actually true-positives. Lastly, an additional performance assessment was conducted using double-platform methods (via a closed-population Huggins mark recapture model) to assess the probability of detection of both the human analyst and automated detector, based on the assumption of false-positive-free and reconciled detections. According to our double-platform analysis, the automated detector performed very well with higher recall and fewer false-positives that the original human analyst.
Interactive effects of climate and land use on pollinator diversity differ among taxa and scales
Authors: Ganuza Cristina , Redlich Sarah , Uhler Johannes , Tobisch Cynthia , Rojas-Botero Sandra , Peters Marcell K. , Zhang Jie , Benjamin Caryl S. , Englmeier Jana , Ewald Jörg , Fricke Ute , Haensel Maria , Kollmann Johannes , Riebl Rebekka , Uphus Lars , Müller Jörg , Steffan-Dewenter Ingolf
Published: May 2022

Changes in climate and land use are major threats to pollinating insects, an essential functional group. Here, we unravel the largely unknown interactive effects of both threats on seven pollinator taxa using a multiscale space-for-time approach across large climate and land-use gradients in a temperate region. Pollinator community composition, regional gamma diversity, and community dissimilarity (beta diversity) of pollinator taxa were shaped by climate-land-use interactions, while local alpha diversity was solely explained by their additive effects. Pollinator diversity increased with reduced land-use intensity (forest < grassland < arable land < urban) and high flowering-plant diversity at different spatial scales, and higher temperatures homogenized pollinator communities across regions. Our study reveals declines in pollinator diversity with land-use intensity at multiple spatial scales and regional community homogenization in warmer and drier climates. Management options at several scales are highlighted to mitigate impacts of climate change on pollinators and their ecosystem services.
Rapid, site-specific labeling of “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains
Authors: Zappala Fabiana , Higbee-Dempsey Elizabeth , Jang Bian , Miller Joann , Yan Lesan , Minutolo Nicholas G. , Rosado González Gabriela T. , Tsourkas Andrew , Ozdemir Burcin Altun
Published: May 2022

Extensive antibody engineering and cloning is typically required to generate new bispecific antibodies. Made-to-order genes, advanced expression systems, and high-efficiency cloning can simplify and accelerate this process, but it still can take months before a functional product is realized. We developed a simple method to site-specifically and covalently attach a T cell–redirecting domain to any off-the-shelf, human immunoglobulin G (IgG) or native IgG isolated from serum. No antibody engineering, cloning, or knowledge of the antibody sequence is required. Bispecific antibodies are generated in just hours. By labeling antibodies isolated from tumor-bearing mice, including two syngeneic models, we generated T cell–redirecting autoantibodies (TRAAbs) that act as an effective therapeutic. TRAAbs preferentially bind tumor tissue over healthy tissue, indicating a previously unexplored therapeutic window. The use of autoantibodies to direct the tumor targeting of bispecific antibodies represents a new paradigm in personalized medicine that eliminates the need to identify tumor biomarkers.
Recall of B cell memory depends on relative locations of prime and boost immunization
Authors: Kuraoka Masayuki , Yeh Chen-Hao , Bajic Goran , Kotaki Ryutaro , Song Shengli , Windsor Ian , Harrison Stephen C. , Kelsoe Garnett
Published: May 2022

Immunization or microbial infection can establish long-term B cell memory not only systemically but also locally. Evidence has suggested that local B cell memory contributes to early local plasmacytic responses after secondary challenge. However, it is unclear whether locality of immunization plays any role in memory B cell participation in recall germinal centers (GCs), which is essential for updating their B cell antigen receptors (BCRs). Using single B cell culture and fate mapping, we have characterized BCR repertoires in recall GCs after boost immunizations at sites local or distal to the priming. Local boosts with homologous antigen recruit the progeny of primary GC B cells to recall GCs more efficiently than do distal boosts. Recall GCs elicited by local boosts contain significantly more B cells with elevated levels of immunoglobulin (Ig) mutation and higher avidity BCRs. This local preference is unaffected by blocking CD40:CD154 interaction to terminate active, GC responses. Local boosts with heterologous antigens elicit secondary GCs with B cell populations enriched for cross-reactivity to the prime and boost antigens; in contrast, cross-reactive GC B cells are rare after distal boosts. Our results suggest that local B cell memory is retained in the form of memory B cells, GC B cells, and GC phenotype B cells that are independent of organized GC structures and that these persistent “primed B cells” contribute to recall GC responses at local sites. Our findings indicate the importance of locality in humoral immunity and inform serial vaccination strategies for evolving viruses.
Chat-ty B cells talk down hematopoiesis
Authors: Elhadi Sapheya H. , Siniscalco Emily R. , Eisenbarth Stephanie C.
Published: May 2022

B cells produce acetylcholine that is sensed by bone marrow stromal cells and reduces hematopoiesis.
Supplemental Material: Detrital zircon ages from upper Paleozoic–Triassic clastic strata on St. Lawrence Island, Alaska: An enigmatic component of the Arctic Alaska–Chukotka microplate
Authors: Amato J.M. , al. et
Published: May 2022

Contains locations of petrographic samples, additional plots for geochronology data, and an Excel file containing all of the U-Pb data tables.  
Robert’s uterus (asymmetric septate uterus): a rare congenital Müllerian duct anomaly
Authors: Dunphy Louise , Taylor Sian , Whitby Elspeth H , Agarwal Umber , Alfirević Žarko
Published: May 2022

Müllerian anomalies such as Robert’s uterus, which was first described by the French gynaecologist Dr Helene Robert in 1969, are rare clinical entities and have been reported in <3% of the female population. Robert’s uterus is a rare phenomenon with a relative dearth of reported cases. Affected individuals may present with pelvic pain and dysmenorrhoea that intensifies near menses or acutely, with severe abdominal pain to the emergency department. They are also associated with adverse pregnancy outcomes, abnormal fetal presentation, preterm labour, recurrent pregnancy loss and infertility. Although ultrasound has a role in its initial assessment, MRI is the best modality to further delineate its anatomy. It is typically managed via laparotomy and total horn resection, endometrectomy of the blind cavity or abdominal metroplasty. The authors present the case of a 40-year-old woman at 19+3 weeks gestation with acute onset of left-sided abdominal pain. A transvaginal ultrasound and MRI of the pelvis confirmed a Robert’s uterus with a viable pregnancy in the upper left horn. She developed a ruptured horn with significant haemoperitoneum. An emergency laparotomy was performed and a non-viable fetus was evident. Only a few cases of pregnancy in the blind hemicavity have been reported so far. This case also highlights the importance of considering this diagnosis in young females presenting with dysmenorrhoea and normal menstrual flow. It is imperative to render a prompt diagnosis, as minimally invasive procedures may be more effective if detected before the formation of adnexal endometriomas.
Delayed, transient quadriplegia; the importance of spinal cord perfusion
Authors: Raper Raymond
Published: May 2022

Transient quadriplegia developed in a man, a short time after, he sustained a cervical spinal fracture in a surfing mishap. The neurological deficit appeared complete, and developed some 30 min after the initial injury in the presence of moderate hypotension. It resolved over a further period of 1–2 hours following restoration of normotension. This case highlights the importance of the maintenance of spinal perfusion pressure in the acute management of traumatic spinal injury.
Acute haematogenous periprosthetic joint infection due toStreptococcus sanguinisalong with coexistent crystalline arthropathy after total knee arthroplasty: a rare combination
Authors: Malkus Joost B , Goedhart Louren M , Verra Wiebe C
Published: May 2022

A man in his 60s, with a medical history of gout, underwent total knee arthroplasty of his right knee followed by expeditious rehabilitation. Seven months after surgery, he was referred to the emergency ward with sudden onset of pain and swelling of his right knee accompanied with fever. Further inquiry revealed no trauma, infection or skin lesions besides a tongue bite several weeks earlier. An impaired range motion of the knee was seen on physical examination along with a tachycardia. Laboratory studies showed a C reactive protein of 345 mg/L, after which a debridement, antibiotics and implant retention procedure was performed. Intraoperatively obtained synovial fluid showed monosodium urate crystals consistent with crystalline arthropathy (ie, gout). However, unexpectedly,Streptococcus sanguiniswas identified in all microbiological cultures too, confirming a coexistent periprosthetic joint infection. After comprehensive antibiotic treatment and gout flare therapy, this patient made a full recovery with retention of the implant.
Prevalence of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease
Authors: Naimimohasses Sara , O'Gorman Philip , McCormick Emma , Ferguson Damien , Monaghan Ann , McGrath Marie , Robinson Mark W , Gormley John , Norris Suzanne
Published: May 2022

Objective

End-stage chronic liver disease is associated with accelerated ageing and increased frailty. Frailty measures have provided clinical utility in identifying patients at increased risk of poor health outcomes, including those awaiting liver transplantation. However, there is limited data on the prevalence and severity of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of frailty and prefrailty in patients with non-cirrhotic NAFLD and correlate with severity of liver disease.

Design

A cross-sectional analysis of functional and laboratory frailty assessments, including the Fried frailty index (FFI), a self-reported frailty index (SRFI) and a lab-based frailty index (FI-LAB), was performed in a cohort of 109 patients with NAFLD, and results compared with fibrosis staging based on transient elastography.

Results

Patients with NAFLD had a high prevalence of prefrailty and frailty, with a median SRFI score of 0.18 (IQR: 0.18), FFI of 1 (IQR: 1) and FI-LAB of 0.18 (IQR: 0.12). Using the SRFI, 45% of F0/F1 patients were classified as prefrail and 20% were classified as frail, while in F2/F3 patients this increased to 36% and 41%, respectively. SRFI, 30 s sit-to-stand and FI-LAB scores increased with increasing liver fibrosis stages (p=0.001, 0.006 and <0.001, respectively). On multivariate linear regression, female gender was identified as a significant predictor of elevated frailty scores.

Conclusion

This study identifies a high prevalence of frailty in individuals with non-cirrhotic NAFLD. Addressing frailty through early rehabilitation interventions may reduce overall morbidity and mortality in this population.
Study designs for clinical trials applied to personalised medicine: a scoping review
Authors: Superchi Cecilia , Brion Bouvier Florie , Gerardi Chiara , Carmona Montserrat , San Miguel Lorena , Sánchez-Gómez Luis María , Imaz-Iglesia Iñaki , Garcia Paula , Demotes Jacques , Banzi Rita , Porcher Raphaël
Published: May 2022

Objective

Personalised medicine (PM) allows treating patients based on their individual demographic, genomic or biological characteristics for tailoring the ‘right treatment for the right person at the right time’. Robust methodology is required for PM clinical trials, to correctly identify groups of participants and treatments. As an initial step for the development of new recommendations on trial designs for PM, we aimed to present an overview of the study designs that have been used in this field.

Design

Scoping review.

Methods

We searched (April 2020) PubMed, Embase and the Cochrane Library for all reports in English, French, German, Italian and Spanish, describing study designs for clinical trials applied to PM. Study selection and data extraction were performed in duplicate resolving disagreements by consensus or by involving a third expert reviewer. We extracted information on the characteristics of trial designs and examples of current applications of these approaches. The extracted information was used to generate a new classification of trial designs for PM.

Results

We identified 21 trial designs, 10 subtypes and 30 variations of trial designs applied to PM, which we classified into four core categories (namely, Master protocol, Randomise-all, Biomarker strategy and Enrichment). We found 131 clinical trials using these designs, of which the great majority were master protocols (86/131, 65.6%). Most of the trials were phase II studies (75/131, 57.2%) in the field of oncology (113/131, 86.3%). We identified 34 main features of trial designs regarding different aspects (eg, framework, control group, randomisation). The four core categories and 34 features were merged into a double-entry table to create a new classification of trial designs for PM.

Conclusions

A variety of trial designs exists and is applied to PM. A new classification of trial designs is proposed to help readers to navigate the complex field of PM clinical trials.
Protocol for updated systematic review and meta-analysis on the burden of non-communicable diseases among people living with HIV in sub-Saharan Africa
Authors: Moyo Maureen , Musekiwa Alfred
Published: May 2022

Introduction

Sub-Saharan Africa (SSA) is faced with the dual epidemics of HIV/AIDS and non-communicable diseases (NCDs). Cardiovascular diseases, cancers, chronic respiratory diseases, diabetes and mental illnesses are the five major NCDs, causing death globally with low-income and middle-income countries, contributing 78% of all NCD deaths and 85% of premature deaths. There has been increased interest in the integration of HIV and NCDs care, especially in SSA that accounts for 55% of people living with HIV (PLHIV) globally. This systematic review and meta-analysis will estimate the overall prevalence or incidence of NCDs (or its risk factors) among adults living with HIV in SSA.

Methods and analysis

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used. Two authors will independently screen the title and abstracts of the articles identified from the search. Study participants will be any adult (≥18 years old) living with HIV in SSA. Exposure of interest will be HIV (with or without ART). Outcomes of interest are prevalence or incidence of any NCD/NCD risk factors. A random-effects meta-analysis will be used to estimate pooled prevalence or incidence of the five major NCDs among PLHIV, using Stata software. χ2 test and I2 statistic will be used to measure statistical heterogeneity between studies. If there is significant heterogeneity, subgroup analysis will be used to investigate potential sources. Publication bias will be assessed using funnel plots and the Stata ‘metabias’ command.

Ethics and dissemination

Ethical review will not be required because it is a systematic review. Data will be kept in the institutional data repository. Study findings will be disseminated through peer-reviewed publications and conference presentations.

PROSPERO registration number

CRD42021258769.
Epicardial injection of allogeneic human-induced-pluripotent stem cell-derived cardiomyocytes in patients with advanced heart failure: protocol for a phase I/IIa dose-escalation clinical trial
Authors: Zhang He , Xue Yunxing , Pan Tuo , Zhu Xiyu , Chong Hoshun , Xu Can , Fan Fudong , Cao Hailong , Zhang Bomin , Pan Jun , Zhou Qing , Yang Gang , Wang Jiaxian , Wang Dong-Jin
Published: May 2022

Introduction

Heart failure (HF) is a growing global public health burden. However, due to the very limited regenerative capacity of mature cardiomyocytes in the adult mammalian heart, conventional treatments can only improve the symptoms of HF but fail to restore cardiac function. Heart transplantation is limited by a severe shortage of donors. Cell-based transplantation for the treatment of HF has become a promising strategy. Human-induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been tested in animal models to assess safety and efficacy. This study aims at evaluating the safety and efficacy of epicardial injection of hiPSC-CMs in patients with advanced HF during coronary artery bypass grafting (CABG) surgery.

Methods

This study is a dose-escalation, placebo-controlled, single-centre phase I/IIa clinical trial. Dose escalation will be guided by a modified 3+3 design for three doses (1×108, 2×108 and 4×108 cells, sequentially). Patients with advanced heart failure will be enrolled and randomly allocated to receive epicardial injection of hiPSC-CMs during CABG surgery or CABG surgery alone, followed by a 12-month follow-up investigation. The primary endpoint is to assess the safety of hiPSC-CMs transplantation, including haemodynamic compromised sustained ventricular arrhythmias and newly formed tumours during 6 months postoperatively. The secondary endpoint is to evaluate the efficacy of epicardial injection of hiPSC-CMs and CABG surgery combination by comparison with CABG surgery alone.

Ethics and dissemination

The study protocol has been approved by the Institutional Ethical Committee of Nanjing Drum Tower Hospital (No. SC202000102) and approved by National Health Commission of the PRC (MR-32-21-014649). Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings.

Trial registration number

NCT03763136.
Evaluating the efficacy and safety of transdermal electrical stimulation on the visual functions of patients with retinitis pigmentosa: a clinical trial protocol for a prospective, multicentre, randomised, double-masked and sham-controlled design (ePICO trial)
Authors: Miura Gen , Ozawa Yoshihito , Shiko Yuki , Kawasaki Yohei , Iwase Takayuki , Fujiwara Tadami , Baba Takayuki , Hanaoka Hideki , Yamamoto Shuichi
Published: May 2022

Introduction

Previously, we conducted a clinical trial to evaluate the safety and efficacy of transdermal electrical stimulation (TdES) with skin electrodes to improve the visual functions in patients with retinitis pigmentosa (RP). No adverse events were related to the treatment during follow-up examinations, and TdES significantly improved the mean visual acuity and visual field sensitivity.

Methods and analysis

We developed a study protocol for a prospective, multicentre, randomised, double-masked and sham-controlled clinical trial, planned to commence on June 2021. We intend to compare the maintenance or improvement in best-corrected visual acuity, and safety of TdES using skin electrodes between patients with RP and the sham group. The primary endpoint comprises the superiority of the logarithm of the minimum angle of resolution (logMAR) visual acuity change at week 24 from baseline in the treatment and sham groups. Secondary endpoints involve the comparison of the treatment and sham groups at week 24 for the logMAR visual acuity, early treatment diabetic retinopathy study visual acuity, the mean deviation value of Humphrey field analyser 10-2, monocular Humphrey Esterman visual field test score, ellipsoid zone length, central foveal thickness and 25-item National Eye Institute Visual Function Questionnaire score. We intend to enrol 50 patients from three Japanese institutions within 1 year and follow them up for 1 years.

Ethics and dissemination

The protocol was approved by the institutional review board at the Chiba University Hospital and two other institutions, and was registered with the Japan Registry of Clinical Trials on 17 May 2021. The trial will be conducted in accordance with the principles of the Declaration of Helsinki, and is in accordance with Good Clinical Practice standards. The findings will be published in a peer-reviewed journal.

Trial registration number

JRCT2032210094.
Psychiatric manifestations and associated risk factors among hospitalised patients with COVID-19 in Edo State, Nigeria: a cross-sectional study
Authors: Okogbenin Esther Osemudiamen , Seb-Akahomen Omonefe Joy , Edeawe Osahogie , Ehimigbai Mary , Eboreime Helen , Odike Angela , Obagaye Michael Olukunle , Aweh Benjamin Efi , Erohubie Paul , Eriyo Williams , Inogbo Chinwe , Akhideno Peter , Eifediyi Gloria , Eifediyi Reuben , Asogun Danny A , Okogbenin Sylvanus
Published: May 2022

Objective

To estimate the prevalence of depression and anxiety and identify associated risk factors in hospitalised persons with confirmed COVID-19 in Edo, Nigeria.

Design

A multicentre cross-sectional survey.

Setting

Patients with COVID-19 hospitalised at the three government-designated treatment and isolation centres in Edo State, Nigeria.

Participants

The study was conducted from 15 April to 11 November 2020 among 489 patients with confirmed COVID-19 and in treatment and isolation centres in Edo State, Nigeria. The mean age of participants was 43.39 (SD=16.94) years. Male participants were 252 (51.5%) and female were 237 (48.5%).

Main outcome measures

The nine-item Patient Health Questionnaire for depression, (total score: 0–27, depression ≥10), Generalized Anxiety Disorder-7 for anxiety (total score: 0–21, anxiety ≥10), and social demographic and clinical characteristics for associated risk factors.

Results

Of the 489 participants, 49.1% and 38.0% had depressive and anxiety symptoms, respectively. The prevalence rates of depression, anxiety and combination of both were 16.2%, 12.9% and 9.0%, respectively. Moderate-severe symptoms of COVID-19, ≥14 days in isolation, worrying about the outcome of infection and stigma increased the risk of having depression and anxiety. Additionally, being separated/divorced increased the risk of having depression and having comorbidity increased the risk of having anxiety.

Conclusion

A substantial proportion of our participants experienced depression, anxiety and a combination of both especially in those who had the risk factors we identified. The findings underscore the need to address modifiable risk factors for psychiatric manifestations early in the course of the disease and integrate mental health interventions and psychosocial support into COVID-19 management guidelines.
Regular feedback to individual endoscopists is associated with improved adenoma detection rate and other key performance indicators for colonoscopy
Authors: Lim Samuel , Tritto Giovanni , Zeki Sebastian , DeMartino Sabina
Published: May 2022

Objective

Monitoring of key performance indicators (KPIs) is a vital element of endoscopy quality improvement. Adenoma detection rate (ADR) is considered the best marker for colonoscopic quality as it inversely correlates with subsequent colonic cancer incidence and mortality, while polyp detection rate (PDR) is an easier-to-calculate surrogate for ADR. This study assessed whether regular feedback to individual endoscopists about their KPIs improved departmental performance.

Methods

Individual KPIs were calculated for a period of 8 years (January 2012–December 2019) and fed back to all endoscopists at 6 monthly intervals, alongside anonymised indicators for other endoscopists, aggregate departmental performance data and benchmarks. An automated natural language processing software (EndoMineR) was used to identify adenomas in pathology reports and calculate ADR. Linear regressions were calculated for departmental ADR, PDR and other KPIs at 6 monthly intervals.

Results

39 359 colonoscopies (average 2460 in every 6-month period, range 1799–3059) were performed by an average of 42 (range 34–50) endoscopists. A continuous improvement in collective performance including ADR (12.7%–21.0%, R20.92, p<0.001) and PDR (19.0%–29.6%, R20.77, p<0.001) was observed throughout the study. Other KPIs showed similar improvement. The detection of non-neoplastic polyps did not increase. When analysed separately, ADR and PDR appeared to improve for gastroenterologists and nurse endoscopists but not for surgeons.

Conclusion

Regular feedback with individual and departmental KPIs was associated with improved ADR and overall performance throughout the 8-year study period. Concomitant monitoring of ADR and PDR may prevent ‘gaming’ behaviour and ensure that genuine improvement is achieved.
Side effects and acceptability measures for thermal ablation as a treatment for cervical precancer in low-income and middle-income countries: a systematic review and meta-synthesis
Authors: Piret Evelyne Marie , Payne Beth A , Smith Laurie W , Trawin Jessica , Orem Jackson , Ogilvie Gina , Nakisige Carolyn
Published: May 2022

Objective

Understanding the side effects and acceptability of thermal ablation (TA) is necessary before large-scale application in screen-and-treat programmes can be justified in low-income and middle-income countries (LMICs).

Design

Articles were selected for inclusion by two independent reviewers. Risk of bias was assessed using the Downs and Black’s criteria. Summary data were extracted, and authors contacted for data when necessary. Proportions of interest and 95% CIs were estimated using a random effects model. Subgroup analysis was performed based on place of treatment and timing of post-treatment follow-up. Heterogeneity was estimated using the I2.

Eligibility criteria

Studies that reported one or more side effects or patient acceptability measures after treatment of the cervix using TA in women living in LMICs who completed a cervical cancer screening test. Included articles were clinical trials or observational studies available in English and published before 18 December 2020.

Information sources

Ovid MEDLINE, EMBASE, CINAHL, CAB Global Health and WHO Global Index Medicus were searched for this systematic review and meta-synthesis.

Results

A total of 1590 abstracts were screened, 84 full text papers reviewed and 15 papers selected for inclusion in the qualitative review, 10 for meta-synthesis (N=2039). Significant heterogeneity was found in screening tests used to identify women eligible for TA and in methods to ascertain side effects. The most commonly reported side effect during treatment was pain (70%, 95% CI 52% to 85%; I2=98.01%) (8 studies; n=1454). No women discontinued treatment due to pain. At treatment follow-up, common side effects included vaginal discharge (72%, 95% CI 18% to 100%; I2=99.55%) (5 studies; n=771) and bleeding (38%, 95% CI 15% to 64%; I2=98.14%) (4 studies; n=856). Satisfaction with treatment was high in 99% (95% CI 98% to 100%; I2=0.00%) of women (3 studies; n=679).

Conclusions

TA results in a number of common side effects, though acceptability remains high among women treated in LMICs. Standardised side effect and acceptability reporting are needed as TA becomes more readily available.

PROSPERO registration number

CRD42020197605.