bluuebunny/crossref_metadata_2025 huggingface dataset:
Population transcriptomic analysis identifies the comprehensive lncRNAs landscape of spike in wheat (Triticum aestivum L.)
Authors: Yang Guang , Deng Pingchuan , Guo Qifan , Shi Tingrui , Pan Wenqiu , Cui Licao , Liu Xiaoqin , Nie Xiaojun
Published: September 2022

Background

Long noncoding RNAs (lncRNAs) are emerging as the important regulators involving in growth and development as well as stress response in plants. However, current lncRNA studies were mainly performed at the individual level and the significance of it is not well understood in wheat.

Results

In this study, the lncRNA landscape of wheat spike was characterized through analysing a total of 186 spike RNA-seq datasets from 93 wheat genotypes. A total of 35,913 lncRNAs as well as 1,619 lncRNA-mRNA pairs comprised of 443 lncRNAs and 464 mRNAs were obtained. Compared to coding genes, these lncRNAs displayed rather low conservation among wheat and other gramineous species. Based on re-sequencing data, the genetic variations of these lncRNA were investigated and obvious genetic bottleneck were found on them during wheat domestication process. Furthermore, 122 lncRNAs were found to act as ceRNA to regulate endogenous competition. Finally, association and co-localization analysis of the candidate lncRNA-mRNA pairs identified 170 lncRNAs and 167 target mRNAs significantly associated with spike-related traits, including lncRNA.127690.1/TraesCS2A02G518500.1 (PMEI) and lncRNA.104854.1/TraesCS6A02G050300.1 (ATG5) associated with heading date and spike length, respectively.

Conclusions

This study reported the lncRNA landscape of wheat spike through the population transcriptome analysis, which not only contribute to better understand the wheat evolution from the perspective of lncRNA, but also lay the foundation for revealing roles of lncRNA playing in spike development.
Alhagi sparsifolia acclimatizes to saline stress by regulating its osmotic, antioxidant, and nitrogen assimilation potential
Authors: Ullah Abd , Tariq Akash , Sardans Jordi , Peñuelas Josep , Zeng Fanjiang , Graciano Corina , Asghar Muhammad Ahsan , Raza Ali , Xiong You-Cai , Chai Xutian , Zhang Zhihao
Published: September 2022

Background

Alhagi sparsifolia (Camelthorn) is a leguminous shrub species that dominates the Taklimakan desert’s salty, hyperarid, and infertile landscapes in northwest China. Although this plant can colonize and spread in very saline soils, how it adapts to saline stress in the seedling stage remains unclear so a pot-based experiment was carried out to evaluate the effects of four different saline stress levels (0, 50, 150, and 300 mM) on the morphological and physio-biochemical responses in A. sparsifolia seedlings.

Results

Our results revealed that N-fixing A. sparsifolia has a variety of physio-biochemical anti-saline stress acclimations, including osmotic adjustments, enzymatic mechanisms, and the allocation of metabolic resources. Shoot–root growth and chlorophyll pigments significantly decreased under intermediate and high saline stress. Additionally, increasing levels of saline stress significantly increased Na+but decreased K+concentrations in roots and leaves, resulting in a decreased K+/Na+ratio and leaves accumulated more Na + and K + ions than roots, highlighting their ability to increase cellular osmolarity, favouring water fluxes from soil to leaves. Salt-induced higher lipid peroxidation significantly triggered antioxidant enzymes, both for mass-scavenging (catalase) and cytosolic fine-regulation (superoxide dismutase and peroxidase) of H2O2. Nitrate reductase and glutamine synthetase/glutamate synthase also increased at low and intermediate saline stress levels but decreased under higher stress levels. Soluble proteins and proline rose at all salt levels, whereas soluble sugars increased only at low and medium stress. The results show that when under low-to-intermediate saline stress, seedlings invest more energy in osmotic adjustments but shift their investment towards antioxidant defense mechanisms under high levels of saline stress.

Conclusions

Overall, our results suggest that A. sparsifolia seedlings tolerate low, intermediate, and high salt stress by promoting high antioxidant mechanisms, osmolytes accumulations, and the maintenance of mineral N assimilation. However, a gradual decline in growth with increasing salt levels could be attributed to the diversion of energy from growth to maintain salinity homeostasis and anti-stress oxidative mechanisms.
Effect of Muller's muscle-conjunctival resection on the upper eyelid crease position in Asian eyelids: a retrospective cohort study
Authors: Chen Hung-Ju , Wang Chun-Yuan , Huang Yu-Fang , Wu Yu-Chieh , Wei Li-Chen
Published: September 2022

Purpose

Investigating the effect of Muller’s muscle-conjunctival resection (MMCR) on the eyelid crease position.

Methods

This retrospective study included patients with unilateral acquired blepharoptosis who underwent MMCR during October 2018–December 2021. The following factors were recorded: preoperative, after phenylephrine, postoperative marginal reflex distance1 (MRD1) and tarsal platform show (TPS) of bilateral eyelids. The primary outcome was to measure the change in TPS and evaluate the factors associated with post-operative TPS. The secondary outcomes included exploring the rate of MRD1 and TPS symmetry after the operation.

Results

Forty patients were included in the final analysis. The mean MRD1 of the ptotic eye was 1.28 ± 0.78 mm, 2.79 ± 0.66 mm and 3.20 ± 0.67 mm before, after phenylephrine and after the operation, respectively. The mean TPS of the ptotic eye was 5.90 ± 1.86 mm, 3.96 ± 1.49 mm and 2.79 ± 1.63 mm before, after phenylephrine and after the operation, respectively. Changes in mean TPS after the phenylephrine test and post-operation were statistically significant (p < 0.001). The linear regression model revealed that the absolute change in TPS after phenylephrine drop and absolute change in MRD1 post-operation were significantly correlated with the absolute change in TPS post-operation. Besides, the ratio of symmetry in MRD1 and TPS was greatly improved post-operation (82.5% and 70.0% respectively).

Conclusion

MMCR is an effective surgical method for ptosis correction as it can not only correct the eyelid crease position but also narrow the wide TPS. This method is particularly beneficial to patients with both mild to moderate ptosis and an asymmetric crease height.
Association between sedentary behavior and depression among South Korean adolescents
Authors: Kim Jinhyun , Kim Hyunkyu , Jang Sung-In , Park Eun-Cheol
Published: September 2022

Background

The symptoms and outcomes of depressed mood are considered severe social issues among Korean adolescents. However, it is difficult to detect depressed mood and evaluate the factors associated with suicide among such individuals. Identifying the risk factors of depressed mood would allow for improved perspectives for interventions. Therefore, in this study, we investigated the association between sedentary behavior and the prevalence of depressed mood.

Methods

From 2014 to 2020, the Korea Youth Risk Behavior Survey (KYRBS), which is a web-based self-report survey, was used for analysis. A total of 366,405 individuals participated in this study. Sedentary behavior was divided into 3 groups based on the duration of sedentary behavior: low sedentary time group (LS, 25 percentile), middle sedentary time group (MS, from 25 to 75 percentile, reference), and high sedentary time group (HS, above 75 percentile). Further, sedentary behavior is divided into 4 subgroups based on weekdays or weekends and owing to studying or non-studying. The chi-square test and multivariate logistic regression were used in this study.

Results

Compared to the MS, which is the reference, male participants in both the LS and HS had experienced depressed mood (adjusted odds ratio (OR): 1.035, 95% CI = 1.003-1.068 in the LS, adjusted OR: 1.091, CI = 1.055-1.129 in the HS). Among females, only the HS was statistically significant (adjusted OR: 1.039, 95% CI = 1.011-1.069 in HS). Korean adolescents with longer sedentary durations during weekdays regardless of the cause of sedentary behavior are positively associated with depressed mood with suicidality in the HS for both genders.

Conclusion

This study found a positive association between the prevalence of depressed mood and sedentary behavior, and it focused on the cause and timing. Interventions targeting sedentary behavior could be effective in reducing depressed mood and suicidality among adolescents.
Exploring pain interference and self-perceived health status in children with osteogenesis imperfecta - a cross-sectional study
Authors: Provenzano Anna Hallin , Åström Eva , Löwing Kristina
Published: September 2022

Background

Chronic pain may affect and interfere in children’s everyday life and can be present in children with Osteogenesis Imperfecta (OI). However, the knowledge is still sparse to what extent pain is present, how pain interfere in children’s everyday life and affect their self-perceived health status. The purpose of the study was therefore to explore presence of chronic pain, pain interference in daily life, and self-perceived health status in children with OI.

Methods

Children with OI, aged 6–18 years, were recruited consecutively to this cross-sectional study. Participants answered a standardised interview including five pre-structured questions, and the Numeric Pain Rating Scale (NPRS), the Pain Interference Index, and a questionnaire concerning self-perceived health status the Patient Reported Outcomes Measurement Information System Pediatric-25 Profile v1.1 (PROMIS-25).

Results

Twenty-eight children (median: 11 years, IQR 6) with OI type I, III, or IV participated. Pain was present in 27 of 28 children and interfered in their everyday life regardless of OI-type, sex, and age. The median NPRS for average pain intensity was 4 (IQR 2), the median for pain frequency was 2–3 times/week, and the median frequency of school absence due to pain was 2–3 times per month. The most common pain locations were back and feet. Pain in the feet was more frequently reported in children with type I (p = 0.032), and pain in the hip was more often reported in children ≥13 years (p = 0.011). The children were asked what they thought to be the cause of pain and the most frequent response was “walking long distances”. Self-perceived health status for mobility was lower than the general population, and lowest for children with type III (p = 0.016). Pain interference was associated with children’s self-perceived health status (rs = 0.84, p < 0.001).

Conclusion

Almost all children experienced pain, which interfered in children’s everyday lives, affected participation in various activities and was associated with reduced self-perceived health status. If children avoid physical activities because of pain, it might cause a vicious circle of inactivity, which further decreases bone density and increase the risk of fractures. The results emphasize the importance to offer adequate pain reducing interventions.
Reliability of a human pose tracking algorithm for measuring upper limb joints: comparison with photography-based goniometry
Authors: Fan Jingyuan , Gu Fanbin , Lv Lulu , Zhang Zhejin , Zhu Changbing , Qi Jian , Wang Honggang , Liu Xiaolin , Yang Jiantao , Zhu Qingtang
Published: September 2022

Background

Range of motion (ROM) measurements are essential for diagnosing and evaluating upper extremity conditions. Clinical goniometry is the most commonly used methods but it is time-consuming and skill-demanding. Recent advances in human tracking algorithm suggest potential for automatic angle measuring from RGB images. It provides an attractive alternative for at-distance measuring. However, the reliability of this method has not been fully established. The purpose of this study is to evaluate if the results of algorithm are as reliable as human raters in upper limb movements.

Methods

Thirty healthy young adults (20 males, 10 females) participated in this study. Participants were asked to performed a 6-motion task including movement of shoulder, elbow and wrist. Images of movements were captured by commercial digital cameras. Each movement was measured by a pose tracking algorithm (OpenPose) and compared with the surgeon-measurement results. The mean differences between the two measurements were compared. Pearson correlation coefficients were used to determine the relationship. Reliability was investigated by the intra-class correlation coefficients.

Results

Comparing this algorithm-based method with manual measurement, the mean differences were less than 3 degrees in 5 motions (shoulder abduction: 0.51; shoulder elevation: 2.87; elbow flexion:0.38; elbow extension:0.65; wrist extension: 0.78) except wrist flexion. All the intra-class correlation coefficients were larger than 0.60. The Pearson coefficients also showed high correlations between the two measurements (p < 0.001).

Conclusions

Our results indicated that pose estimation is a reliable method to measure the shoulder and elbow angles, supporting RGB images for measuring joint ROM. Our results presented the possibility that patients can assess their ROM by photos taken by a digital camera.

Trial registration

This study was registered in the Clinical Trials Center of The First Affiliated Hospital, Sun Yat-sen University (2021–387).
Using implementation science frameworks to translate and adapt a pregnancy app for an emerging Latino community
Authors: Castillo Anabel F. , Davis Alexander L. , Krishnamurti Tamar
Published: September 2022

Background

Digital mobile health (mHealth) applications are a popular form of prenatal education and care delivery in the U.S.; yet there are few Spanish language options for native speakers. Furthermore, existing applications do not consider cultural differences and disparities in healthcare access, including those specific to emerging Latino communities.

Objective

To adapt and translate an English-language pregnancy mobile health app to meet the language and cultural needs of Spanish-speaking Latino immigrants living in the United States.

Methods

We use a multi-step process, grounded in implementation science frameworks, to adapt and translate the contents of an existing pregnancy app. Interviews with stakeholders (n = 12) who advocate for the needs of pregnant individuals in an emerging Latino community were used to identify domains of possible disparities in access to prenatal care. We then conducted semi-structured interviews with peripartum Spanish-speaking Latino users (n = 14) to understand their perspectives within those domains. We identified a list of topics to create educational material for the modified app and implemented a systematic translation approach to ensure that the new version was acceptable for immigrants from different countries in Latin America.

Results

The interviews with stakeholders revealed seven critical domains that need to be addressed in an adapted prenatal app: language and communication, financial concerns, social support, immigration status, cultural differences, healthcare navigation, and connection to population-specific community resources that offer Spanish language services. The interviews with peripartum Spanish-speaking Latino women informed how the existing content in the app could be adjusted or built upon to address these issues, including providing information on accessing care offered in their native language and community support. Finally, we used a systematic approach to translate the existing application and create new content.

Conclusion

This work illustrates a process to adapt an mHealth pregnancy app to the needs of an emerging Latino community, by incorporating culturally sensitive Spanish language content while focusing on addressing existing health disparities.
Exploring how biobanks communicate the possibility of commercial access and its associated benefits and risks in participant documents
Authors: Samuel G. , Hardcastle F. , Broekstra R. , Lucassen A.
Published: September 2022

Background

Biobanks and biomedical research data repositories collect their samples and associated data from volunteer participants. Their aims are to facilitate biomedical research and improve health, and they are framed in terms of contributing to the public good. Biobank resources may be accessible to researchers with commercial motivations, for example, researchers in pharmaceutical companies who may utilise the data to develop new clinical therapeutics and pharmaceutical drugs. Studies exploring citizen perceptions of public/private interactions associated with large health data repositories/biobanks indicate that there are sensitivities around public/private and/or non-profit/profit relationships and international sample and data sharing. Less work has explored how biobanks communicate their public/private partnerships to the public or to their potential research participants.

Methods

We explored how a biobank’s aims, benefits and risks, and private/public relationships have been framed in public facing recruitment documents (consent forms and participant information sheets).

Results

Biobank documents often communicate their commercial access arrangements but not the detail about what these interactions would entail, and how risks and benefits would be distributed to the public.

Conclusion

We argue that this leads to a polarised discourse between public and private entities and/or activities, and fails to attend to the blurred lines between them. This results in a lack of attention to more important issues such as how risks and benefits in general are distributed to the public. We call for a nuanced approach that can contribute to the much-needed dialogue in this space.
Psychometric properties and latent profile analysis of the Nursing Brand Image Scale: a methodological study in the Chinese context
Authors: Zhou Lu , Ni Zhao , Godsey Judi Allyn , Sukpasjaroen Khunanan , Wu YuMing , Liu Gao , Chankoson Thitinan , Kallmeyer Robert , Cai EnLi
Published: September 2022

Aims

To translate the U.S. version of the Nursing Brand Image Scale to Chinese (NBIS-C) and evaluate its psychometric properties when administered to a national sample of Chinese nurses, and identify nursing brand image profiles in Chinese nurses.

Design

A cross-sectional study was conducted to validate the NBIS-C among nurses in China.

Methods

The psychometric properties of the NBIS-C were tested in accordance with the COSMIN checklist. The reliability, validity, and responsiveness of the 42-item NBIS-C were examined in a national sample of 759 nurses recruited from 29 Chinese provinces. Latent Profile Analyses (LPA) were conducted to reveal nurses’ perceptions of the brand image of nursing.

Results

Results of this study demonstrated acceptable validity (content validity, structural validity, and construct validity), reliability (internal consistency and test-retest reliability), adequate responsiveness, and no floor/ceiling effect of the NBIS-C. LPA yielded five subgroups: Integrated, Traditional, Subordinate, Creative and Leader.

Conclusion

The psychometric properties of the NBIS-C are suitable for assessing the image of nursing among Chinese nurses. Future studies with a larger, more diverse sample are recommended. Although the role of nurses in China has evolved, nurses in general have failed to communicate a consistent, positive, and accurate brand image for the nursing profession.
Development of a performance measurement system for general practitioners’ office in China’s primary healthcare
Authors: Ruan Wenjie , Liu Changming , Liao Xiaoyang , Guo Zhaoxia , Zhang Yalin , Lei Yi , Chen Huadong
Published: September 2022

Background

General practitioners are the main providers of primary care services. To better strengthen the important role of general practitioners in primary healthcare services, China is promoting the general practitioners’ office system. There is a lack of well-accepted methods to measure the performance of general practitioner offices in China. We thus aim to develop a systematic and operable performance measurement system for evaluating the general practitioner’s office.

Methods

We establish an index pool of the performance measurement system of general practitioners’ offices by a cross-sectional study and the literature research method and adopt the focus group method to establish the preliminary system. The Delphi method is then used to conduct three rounds of consultation to modify indices, which aims to form the final indicator system. We determine the weight of each index by the analytic hierarchy process method, which together with the final indicator system constitutes the final performance measurement system. Finally, we select three offices from three different cities in Sichuan Province, China, as case offices to conduct the case study, aiming to assess its credibility.

Results

Our results show that the first office scored 958.5 points, the second scored 768.1 points, and the third scored 947.7 points, which corresponds to the reality of these three offices, meaning that the performance measurement system is effective and manoeuvrable.

Conclusions

Our study provides support for standardizing the functions of China’s general practitioner’s office, improving the health service quality of generalists, and providing a theoretical basis for the standardization of the general practitioner’s office.
Effectiveness of early essential newborn care implementation in four counties of western China
Authors: Wang Chenran , Lin Yun , Zhang Hanxiyue , Yang Ge , Tang Kun , Tian Xiaobo , Huang Xiaona , Xu Tao
Published: September 2022

Background

Neonatal survival is a public health concern globally. However, the regional disparity in neonatal mortality between rural counties of western China and urban areas of eastern provinces remains high. Early essential newborn care (EENC), recommended by World Health Organization, refers to a set of cost-effective interventions to improve neonatal health and development outcomes. In this study, we aimed to explore the effectiveness of EENC implementation in four counties of western China.

Methods

Pre- and post-intervention investigations were conducted in four selected EENC intervention counties and four control counties of four western provinces of China, from June to August 2017 and from December 2020 to April 2021 respectively. A mixed quantitative and qualitative approach was used for data collection and analysis. Data on the coverage of EENC practices were collected via a post-intervention face-to-face questionnaire survey with postpartum mothers before hospital discharge. Hospital-reported data on neonatal health indicators were obtained through mail surveys in both investigations. We also performed semi-structured interviews with policymakers, health staff and postpartum mothers to understand their perceptions about the usefulness of EENC implementation.

Results

Overall, 599 mother-newborn pairs in the intervention group and 699 pairs in the control group participated in the post-intervention survey. Controlling for the confounding factor of province, the proportion of newborns receiving EENC interventions was higher in the intervention group than in the control group (P < 0.05). Intervention groups in four provinces had higher coverage of: any skin-to-skin contact (99.50% vs. 49.07%); early breastfeeding initiation (within 60 min of birth) (90.84% vs. 80.35%); no medicine applied to the umbilical cord (98.50% vs. 9.73%); routine eye care (93.16% vs. 8.73%); and vitamin K1 administration (98.33% vs. 88.98%). EENC implementation was associated with decreased risk of neonatal diarrhea (OR: 0.326, 95% CI: 0.123, 0.865) and eye infection (OR: 0.147, 95% CI: 0.045, 0.483). Policymakers, health staff and postpartum mothers expressed satisfaction with the EENC interventions, noting a willingness among staff and policymakers to implement and sustain these interventions; the promotion of these interventions within hospital policy; the positive emotions experienced by postpartum mothers; perceived improvements in health; and improvements in support for health workers.

Conclusion

EENC-recommended core practices (except kangaroo mother care) have been successfully introduced in pilot hospitals. The efficacy of EENC implementation should be highly recognized to accelerate the progress towards its national roll out.
Immune cell composition of the bronchoalveolar lavage fluid in healthy and respiratory diseased dromedary camels
Authors: Shawaf Turke , Schuberth Hans-Joachim , Hussen Jamal
Published: September 2022

Background

Respiratory diseases are among the most common and expensive to treat diseases in camels with a great economic impact on camel health, welfare, and production. Bronchoalveolar lavage fluid (BALF) has been proven as a valuable sample for investigating the leukocyte populations in the respiratory tract of several species. In the present study, fluorescent antibody labeling and flow cytometry were used to study the immune cell composition of BALF in dromedary camels. Animals with clinical respiratory diseases (n = seven) were compared with apparently healthy animals (n = 10). In addition, blood leukocytes from the same animals were stained in parallel with the same antibodies and analyzed by flow cytometry.

Results

Camel BALF macrophages, granulocytes, monocytes, and lymphocytes were identified based on their forward and side scatter properties. The expression pattern of the cell markers CD172a, CD14, CD163, and MHCII molecules on BALF cells indicates a similar phenotype for camel, bovine, and porcine BALF myeloid cells. The comparison between camels with respiratory disease and healthy camels regarding cellular composition in their BALF revealed a higher total cell count, a higher fraction of granulocytes, and a lower fraction of macrophages in diseased than healthy camels. Within the lymphocyte population, the percentages of helper T cells and B cells were also higher in diseased than healthy camels. The elevated expression of the activation marker CD11a on helper T cells of diseased camels is an indication of the expansion of helper T cells population due to infection and exposure to respiratory pathogens. The higher abundance of MHCII molecules on BALF macrophages from diseased camels indicates a polarization toward an inflammatory macrophage phenotype (M1) in respiratory diseased camels. No significant differences were observed in the systemic leukogram between healthy and diseased animals.

Conclusions

Collectively, the current study represents the first report on flow cytometric analysis of immune cell composition of bronchoalveolar lavage fluid (BALF) in dromedary camels.
Nicotinamide reverses deficits in puberty-born neurons and cognitive function after maternal separation
Authors: Hao Keke , Wang Huiling , Zhang Yuejin , Xie Xinhui , Huang Huan , Chen Cheng , Xu Shilin , Xu Rui , Shu Chang , Liu Zhongchun , Zhou Yuan , Reynolds Gavin P. , Wang Gaohua
Published: September 2022

Background

Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS.

Methods

Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins.

Results

Compared with controls, only MS animals in the adult stage (PND56–65) but not the adolescent stage (PND31–40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1β, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35–65).

Conclusions

MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.
ParticleChromo3D: a Particle Swarm Optimization algorithm for chromosome 3D structure prediction from Hi-C data
Authors: Vadnais David , Middleton Michael , Oluwadare Oluwatosin
Published: September 2022

Background

The three-dimensional (3D) structure of chromatin has a massive effect on its function. Because of this, it is desirable to have an understanding of the 3D structural organization of chromatin. To gain greater insight into the spatial organization of chromosomes and genomes and the functions they perform, chromosome conformation capture (3C) techniques, particularly Hi-C, have been developed. The Hi-C technology is widely used and well-known because of its ability to profile interactions for all read pairs in an entire genome. The advent of Hi-C has greatly expanded our understanding of the 3D genome, genome folding, gene regulation and has enabled the development of many 3D chromosome structure reconstruction methods.

Results

Here, we propose a novel approach for 3D chromosome and genome structure reconstruction from Hi-C data using Particle Swarm Optimization (PSO) approach called ParticleChromo3D. This algorithm begins with a grouping of candidate solution locations for each chromosome bin, according to the particle swarm algorithm, and then iterates its position towards a global best candidate solution. While moving towards the optimal global solution, each candidate solution or particle uses its own local best information and a randomizer to choose its path. Using several metrics to validate our results, we show that ParticleChromo3D produces a robust and rigorous representation of the 3D structure for input Hi-C data. We evaluated our algorithm on simulated and real Hi-C data in this work. Our results show that ParticleChromo3D is more accurate than most of the existing algorithms for 3D structure reconstruction.

Conclusions

Our results also show that constructed ParticleChromo3D structures are very consistent, hence indicating that it will always arrive at the global solution at every iteration. The source code for ParticleChromo3D, the simulated and real Hi-C datasets, and the models generated for these datasets are available here:https://github.com/OluwadareLab/ParticleChromo3D
A multi-point constraint unfitted finite element method
Authors: Freeman Brubeck Lee
Published: September 2022

In this work a multi-point constraint unfitted finite element method for the solution of the Poisson equation is presented. Key features of the approach are the strong enforcement of essential boundary, and interface conditions. This, along with the stability of the method, is achieved through the use of multi-point constraints that are applied to the so-called ghost nodes that lie outside of the physical domain. Another key benefit of the approach lies in the fact that, as the degrees of freedom associated with ghost nodes are constrained, they can be removed from the system of equations. This enables the method to capture both strong and weak discontinuities with no additional degrees of freedom. In addition, the method does not require penalty parameters and can capture discontinuities using only the standard finite element basis functions. Finally, numerical results show that the method converges optimally with mesh refinement and remains well conditioned.
Malaria research in the Central African Republic from 1987 to 2020: an overview
Authors: Nzoumbou-Boko Romaric , Velut Guillaume , Imboumy-Limoukou Romeo-Karl , Manirakiza Alexandre , Lekana-Douki Jean-Bernard
Published: September 2022

Background

The national malaria control policy in the Central African Republic (CAR) promotes basic, clinical, and operational research on malaria in collaboration with national and international research institutions. Preparatory work for the elaboration of National Strategic Plans for the implementation of the national malaria control policy includes developing the research component, thus requiring an overview of national malaria research. Here, this survey aims to provide an inventory of malaria research as a baseline for guiding researchers and health authorities in choosing the future avenues of research.

Methods

Data sources and search strategy were defined to query the online Medline/PubMed database using the “medical subject headings” tool. Eligibility and study inclusion criteria were applied to the selected articles, which were classified based on year, research institute affiliations, and research topic.

Results

A total of 118 articles were retrieved and 51 articles were ultimately chosen for the bibliometric analysis. The number of publications on malaria has increased over time from 1987 to 2020. These articles were published in 32 different journals, the most represented being the Malaria Journal (13.73%) and the American Journal of Tropical Medicine and Hygiene (11.76%). The leading research topics were drug evaluation (52.94%), expatriate patients (23.54%), malaria in children (17.65%), morbidity (13.7%), and malaria during pregnancy (11.76%). The publications’ authors were mainly affiliated with the Institut Pasteur of Bangui (41%), the French Military Medical Service (15.5%), and the University of Bangui (11.7%). Collaborations were mostly established with France, the UK, and the USA; some collaborations involved Switzerland, Austria, Pakistan, Japan, Sri Lanka, Benin, Cameroun, Ivory Coast, and Madagascar. The main sources of research funding were French agencies (28.6%) and international agencies (18.3%). Most studies included were not representative of the whole country. The CAR has the capacity to carry out research on malaria and to ensure the necessary collaborations.

Conclusion

Malaria research activities in the CAR seem to reflect the priorities of national policy. One remaining challenge is to develop a more representative approach to better characterize malaria cases across the country. Finally, future research and control measures need to integrate the effect of COVID-19.
Impact of COVID-19 pandemic on physical and mental health status and care of adults with epilepsy in Germany
Authors: Körbel Kimberly , Rosenow Felix , Maltseva Margarita , Müller Heiko , Schulz Juliane , Tsalouchidou Panagiota-Eleni , Langenbruch Lisa , Kovac Stjepana , Menzler Katja , Hamacher Mario , von Podewils Felix , Willems Laurent M. , Mann Catrin , Strzelczyk Adam
Published: September 2022

Background

To mitigate the potential consequences of the coronavirus disease 2019 (COVID-19) pandemic on public life, the German Federal Government and Ministry of Health enacted a strict lockdown protocol on March 16, 2020. This study aimed to evaluate the impact of the COVID-19 pandemic on physical and mental health status and the supply of medical care and medications for people with epilepsy (PWE) in Germany.

Methods

The Epi2020 study was a large, multicenter study focused on different healthcare aspects of adults with epilepsy. In addition to clinical and demographic characteristics, patients were asked to answer a questionnaire on the impact of the first wave of the COVID-19 pandemic between March and May 2020. Furthermore, the population-based number of epilepsy-related admissions in Hessen was evaluated for the January-June periods of 2017–2020 to detect pandemic-related changes.

Results

During the first wave of the pandemic, 41.6% of PWE reported a negative impact on their mental health, while only a minority reported worsening of their seizure situation. Mental and physical health were significantly more negatively affected in women than men with epilepsy and in PWE without regular employment. Moreover, difficulties in ensuring the supply of sanitary products (25.8%) and antiseizure medications (ASMs; 19.9%) affected PWE during the first lockdown; no significant difference regarding these impacts between men and women or between people with and without employment was observed. The number of epilepsy-related admissions decreased significantly during the first wave.

Conclusions

This analysis provides an overview of the general and medical care of epilepsy patients during the COVID-19 pandemic. PWE in our cohort frequently reported psychosocial distress during the first wave of the pandemic, with significant adverse effects on mental and physical health. Women and people without permanent jobs especially reported distress due to the pandemic. The COVID‐19 pandemic has added to the mental health burden and barriers to accessing medication and medical services, as self-reported by patients and verified in population-based data on hospital admissions.

Trial registration

German Clinical Trials Register (DRKS), DRKS00022024. Registered October 2, 2020, http://www.drks.de/DRKS00022024
Emerging Therapies for the Management of Richter Transformation
Authors: Smyth Elizabeth , Eyre Toby A. , Cheah Chan Y.
Published: September 2022

Richter transformation (RT) refers to the development of an aggressive lymphoma in patients with underlying chronic lymphocytic leukemia/small lymphocytic lymphoma. Aside from a small subgroup of patients with clonally unrelated and previously untreated chronic lymphocytic leukemia, the disease responds poorly to standard therapies and prognosis is dismal. Recent developments in the understanding of the biology of RT and the advent of several targeted agents may result in improved outcomes for these patients. The purpose of this review is to analyze recent data on the pathogenesis and treatment of RT. We reviewed studies addressing the pathophysiology of RT and analyzed the data for frontline chemoimmunotherapy and emerging targeted therapies likely to play a significant role in the future management of RT. Several biologic and clinical factors may help identify those who are unlikely to respond to conventional chemoimmunotherapy; where possible, these patients should be managed with a novel approach. Emerging therapies for the management of RT include chimeric antigen receptor T-cell therapy, noncovalent Bruton tyrosine kinase inhibitors, and T‐cell–engaging bispecific antibodies. The use of less toxic and more effective targeted therapies may result in improved outcomes. Larger, prospective clinical trials are required to confirm efficacy and safety of novel agents for the management of RT, particularly when used in combination with other targeted therapies and in addition to chemoimmunotherapy regimens.
Chimeric Antigen Receptor T-Cell Therapies: Barriers and Solutions to Access
Authors: Mikhael Joseph , Fowler Jessica , Shah Nina
Published: September 2022

Chimeric antigen receptor T-cell (CAR-T) therapies are relatively new treatments for patients with heavily pretreated hematologic malignancies. Although these innovative therapies can offer substantial benefit to patients with limited alternative treatment options, patient-access barriers exist. Conventional clinical trials are time-consuming and may be limited by strict patient eligibility criteria, resources, and availability of enrollment slots. Because of the complexity of the CAR-T administration process, treatment delivery can be associated with additional burden for the patient, including requiring patients to reside close to treatment centers and remain with a caregiver after infusion. Manufacturing of CAR-T cells is completed in specialized facilities and depends on the availability of reagents, manufacturing workforce, and timely transportation. CAR-T therapy is costly, and many US health plans restrict coverage of cell and gene therapies. Several of the existing challenges because of these barriers have been exacerbated during the COVID-19 pandemic. This review discusses these barriers and proposes some potential solutions to improving patient access, including innovation in clinical trial design and manufacturing, location of treatment delivery, and key stakeholder opinions regarding treatment and reimbursement. We propose a call to action for key stakeholder groups to address these barriers to CAR-T therapy to expand treatment access for patients. Future collaboration between key stakeholders, including payers, regulatory agencies, and industry/academia, will be critical to continue to address these barriers and enhance patient access to these therapies.
BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma
Authors: van Not Olivier J. , Blokx Willeke A.M. , van den Eertwegh Alfons J.M. , de Meza Melissa M. , Haanen John B. , Blank Christian U. , Aarts Maureen J.B. , van den Berkmortel Franchette W.P.J. , de Groot Jan Willem B. , Hospers Geke A.P. , Kapiteijn Ellen , Piersma Djura , van Rijn Rozemarijn S. , Stevense-den Boer Marion , van der Veldt Astrid A.M. , Boers-Sonderen Marye J. , Jansen Anne M.L. , Wouters Michel W.J.M. , Suijkerbuijk Karijn P.M.
Published: September 2022

PURPOSE

Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma.

MATERIALS AND METHODS

All patients with advanced melanoma treated with first-line anti–PD-1 or ipilimumab-nivolumab between 2012 and 2021 in the nationwide Dutch Melanoma Treatment Registry were included in this cohort study. Objective response rate, progression-free survival (PFS), and overall survival (OS) were analyzed according to BRAF and NRAS status. A multivariable Cox model was used to analyze prognostic factors associated with PFS and OS.

RESULTS

In total, 1764 patients received anti–PD-1 and 759 received ipilimumab-nivolumab. No significant differences in PFS were found in the anti–PD-1 cohort. In the ipilimumab-nivolumab cohort, median PFS was significantly higher for BRAF-mutant melanoma (9.9 months; 95% CI, 6.8 to 17.2) compared with NRAS-mutant (4.8 months; 95% CI, 3.0 to 7.5) and double wild-type (5.3 months; 95% CI, 3.6 to 7.1). In multivariable analysis, BRAF-mutant melanoma was significantly associated with a lower risk of progression or death in the ipilimumab-nivolumab cohort. Median OS was significantly higher for BRAF-mutant melanoma compared with NRAS-mutant and double wild-type melanoma for both immune checkpoint inhibitor regimens.

CONCLUSION

Ipilimumab-nivolumab–treated patients with BRAF-mutant melanoma display improved PFS and OS compared with patients with NRAS-mutant and double wild-type melanoma. BRAF mutation status is a factor to consider while choosing between mono and dual checkpoint inhibition in advanced melanoma.
Sex Differences in the Molecular Programs of Pancreatic Cells Contribute to the Differential Risks of Type 2 Diabetes
Authors: Yong Hyo Jeong , Toledo Maria Pilar , Nowakowski Richard S , Wang Yue J
Published: September 2022

Epidemiology studies demonstrate that women are at a significantly lower risk of developing type 2 diabetes (T2D) compared to men. However, the molecular basis of this risk difference is not well understood. In this study, we examined the sex differences in the genetic programs of pancreatic endocrine cells. We combined pancreas perifusion data and single-cell genomic data from our laboratory and from publicly available data sets to investigate multiple axes of the sex differences in the human pancreas at the single-cell type and single-cell level. We systematically compared female and male islet secretion function, gene expression program, and regulatory principles of pancreatic endocrine cells. The perifusion data indicate that female endocrine cells have a higher secretion capacity than male endocrine cells. Single-cell RNA-sequencing analysis suggests that endocrine cells in male controls have molecular signatures that resemble T2D. In addition, we identified genomic elements associated with genome-wide association study T2D loci to have differential accessibility between female and male delta cells. These genomic elements may play a sex-specific causal role in the pathogenesis of T2D. We provide molecular mechanisms that explain the differential risk of T2D between women and men. Knowledge gained from our study will accelerate the development of diagnostics and therapeutics in sex-aware precision medicine for diabetes.
Health in Ruins
Authors: Abadía-Barrero César Ernesto
Published: September 2022

In Health in Ruins César Ernesto Abadía-Barrero chronicles the story of El Materno—Colombia’s oldest maternity and neonatal health center and teaching hospital—over several decades as it faced constant threats of government shutdown. Using team-based and collaborative ethnography to analyze the social life of neoliberal health policy, Abadía-Barrero details the everyday dynamics around teaching, learning, and working in health care before, during, and after privatization. He argues that health care privatization is not only about defunding public hospitals; it also ruins rich traditions of medical care by denying or destroying ways of practicing medicine that challenge Western medicine. Despite radical cuts in funding and a corrupt and malfunctioning privatized system, El Materno’s professors, staff, and students continued to find ways to provide innovative, high-quality, and noncommodified health care. By tracking the violences, conflicts, hopes, and uncertainties that characterized the struggles to keep El Materno open, Abadía-Barrero demonstrates that any study of medical care needs to be embedded in larger political histories.
Predictors of Subsequent Intervention After Middle Meningeal Artery Embolization for Treatment of Subdural Hematoma: A Nationwide Analysis
Authors: Fuentes Angelica M. , Khalid Syed I. , Mehta Ankit I.
Published: September 2022

BACKGROUND:

Middle meningeal artery (MMA) embolization has recently emerged as an effective technique to treat subdural hematomas (SDHs). Studies to date have been limited, largely, to single-center studies with limited follow-up and have not assessed subsequent surgical interventions and factors associated with these interventions.

OBJECTIVE:

To evaluate rates of retreatment for SDH after MMA embolization and patient-specific factors that may be important predictors for these interventions.

METHODS:

Using an all-payer claims database, Mariner, patients who underwent MMA embolization between January 2010 and October 2020 after the diagnosis of SDH were identified. Rates of post-MMA embolization surgical interventions, including craniotomy and burr hole drainage, were accessed within 5 years following. Patient-specific contributors to the rates of these interventions were studied using Gaussian logistic regression models.

RESULTS:

A total of 322 patients were included. Of this cohort, 55 (17.1%) required subsequent intervention within 5 years, with 36 (11.2%) receiving burr hole evacuation and 19 (5.9%) receiving craniotomy. Factor Xa inhibitor use was independently associated with subsequent interventions after MMA embolization procedures (odds ratio: 1.20 [95% CI: 1.02-1.40]). Of the other patient factors evaluated, including age, sex, comorbidity status, and use of vitamin K antagonists, antiplatelets, and factor Xa inhibitors, none were found to be significantly associated with future interventions.

CONCLUSION:

Although previous literature has shown MMA embolization to be safe and successful in preventing recurrent SDH, patients undergoing this procedure still carry a risk of future interventions. Patients taking factor Xa inhibitors are at especially high risk of subsequent intervention after MMA embolization.