bluuebunny/crossref_metadata_2025 huggingface dataset:
Change in waist circumference and lifestyle habit factors as a predictor of metabolic risk among middle-aged and elderly Japanese people: population-based retrospective 10-year follow-up study from 2008 to 2017
Authors: Ono Haruko , Akahoshi Kotomi , Kai Michiaki
Published: March 2022

Background

Waist circumference (WC) increases more than body mass index (BMI) over time. This study investigated the change in WC among middle-aged and elderly Japanese people for 10 years, and its relationship with lifestyle and lipid metabolism factor.

Methods

Health checkup data and lifestyle habits of a retrospective cohort of 745 people aged 40–65 years who underwent health checkups at least three times between 2008 and 2017 were analyzed. Information of Lifestyle habits about smoking history, regular exercise, alcohol intake skipping breakfast was collected using a self-administered questionnaire. Participants who were taking medications for diabetes, hyperlipidemia, or hypertension were excluded from analyses. Longitudinal associations between the change in WC and lifestyle habit factors with adjustments for sex, age, and WC at the start of health checkups were assessed using generalized linear models.

Results

Regardless of lifestyle, body weight (BW) decreased 0.8 kg (p < 0.001) for women, 0.9 kg (p = 0.003) for men, WC increased 0.8 cm (p = 0.007) for women, 0.2 cm (p = 0.657) for men. In addition, serum triglycerides and high- and low-density lipoprotein levels estimated 10 years later revealed that increased WC ratios also exacerbated the respective blood sample data.

Conclusion

Both men and women showed an increase in WC regardless of BW changes, and the increase in WC worsened lipid metabolism. For the middle-aged and elderly, whose WC increases over time, it will be more important to take notice of their WC than BW or BMI for effective health checkups.
The status of infection prevention and control structures in Eastern China based on the IPCAF tool of the World Health Organization
Authors: Ni Kaiwen , Jin Dingping , Wu Zhe , Sun Liyuan , Lu Qun
Published: March 2022

Background

The burden of healthcare-associated infections (HAIs) and the spread of antimicrobial resistance can be potentially preventable through comprehensive infection prevention and control (IPC) programs. However, information on the current state of IPC implementation is rare in China.

Methods

A cross-sectional study was conducted in Zhejiang province, China, from April to June 2021. The Zhejiang nosocomial infection control and quality improvement center (NICQI) cooperated with 11 municipal NICQI centers to introduce the purpose of this study and invite all licensed secondary and tertiary hospitals in Zhejiang province through WeChat group. The questionnaire had three sections, including information about participating hospitals, demographic information about IPs, and the Chinese version of the Infection Prevention and Control Assessment Framework that covered eight core components (CC).

Results

Of the 382 hospitals invited, 222 (58.1% response rate) accepted and completed the online questionnaire. The overall median score of the participating hospitals was 682 (630–723), which corresponded to an advanced level of IPC. There was a significant difference in scores between hospitals types (P < 0.001). Profound differences were revealed regarding the scores of the individual components, with CC2 (IPC guidelines) and CC6 (Monitoring/audit of IPC practices and feedback) having the highest (100) and lowest (65) median scores, respectively. Only 23 (10.4%) hospitals reported assessing facility safety culture.

Conclusions

IPC structures are at a relatively high level in acute care hospitals in Eastern China. The identified potential areas for improvement were similar to those identified in developed countries, particularly regarding multimodal strategies for implementation and safety culture construction. Meanwhile, the Chinese government should pay more attention to IPC resources and practices among secondary care hospitals.
Association between fat mass by bioelectrical impedance analysis and bone mass by quantitative ultrasound in relation to grip strength and serum 25-hydroxyvitamin D in postmenopausal Japanese women: the Unzen study
Authors: Mizukami Satoshi , Arima Kazuhiko , Abe Yasuyo , Tomita Yoshihito , Nakashima Hiroki , Honda Yuzo , Uchiyama Michiko , Ookawachi Tetsuji , Goto Hisashi , Hasegawa Maiko , Sou Youko , Kanagae Mitsuo , Osaki Makoto , Aoyagi Kiyoshi
Published: March 2022

Background

Whether fat mass or lean mass affects bone mass in postmenopausal women is controversial. This study aimed to explore the association between body composition measured by bioelectrical impedance analysis (BIA) and bone mass measured by quantitative ultrasound (QUS) in postmenopausal women in Japan.

Methods

We conducted a cross-sectional study, The Unzen Study, on 382 community-dwelling postmenopausal Japanese women (mean (standard deviation) age: 68.2 (7.2) years) who participated in periodic health examinations. The stiffness index (SI) was measured using QUS, and body composition (e.g., fat mass and muscle mass) was measured using BIA. Grip strength was measured. Fasting blood samples were collected, and 25-hydroxyvitamin D (25(OH)D), tartrate-resistant acid phosphatase-5b (TRACP-5b), and parathyroid hormone (PTH) levels were measured. Data on current smoking, alcohol consumption, exercise, and any comorbidities (heart disease, lung disease, stroke, or diabetes mellitus) were collected.

Results

The SI increased with increasing quartiles of fat mass and muscle mass (both p for trend <  0.001), respectively. There were positive correlations between SI and log (25(OH)D) or grip strength. Fat mass significantly correlated with grip strength. Multiple linear regression analysis showed that higher fat mass was independently and significantly associated with higher SI after adjusting for age, height, comorbidity, current smoking, alcohol consumption, exercise, log (25(OH)D), log (TRACP-5b), log (PTH), and grip strength (p = 0.001). In contrast, no association was observed between muscle mass and SI.

Conclusions

Fat mass, but not muscle mass, was a significant determinant of SI in community-dwelling postmenopausal Japanese women.
In situ XRF investigations to unravel the provenance area of Corinthian ware from excavations in Milazzo (Mylai) and Lipari (Lipára)
Authors: Belfiore Cristina M. , Mastelloni Maria A. , Barone Germana , Mazzoleni Paolo
Published: March 2022

In this contribution a non-destructive approach has been used aiming at investigating the chemical composition of 35 ceramic items belonging to the collections of the Regional Aeolian Museum “Luigi Bernabò Brea” in the Lipari Island (Sicily, Italy). Different vessel types have been selected for analysis, including aryballoi, kotylai, olpai, anforiskoi, oinochoai, and alabastra, belonging to the “Proto-Corinthian and Corinthian” ware classes. The items, dating back to the period comprised between the early eighth and the first half of the sixth century BC, come from two different archaeological sites in the province of Messina (Sicily), specifically the Istmo necropolis of Milazzo, in the northern Sicilian coast, and the acropolis and necropolis of Lipari, in the Aeolian islands. The chemical characterization of ceramics, carried out through portable X-ray fluorescence spectroscopy (pXRF), aimed at gaining information on the production area of examined items whose autoptic analysis pointed to Corinthian imports. The possibility of carrying out experimental investigations on the most ancient materials from the archaic necropolis of Milazzo and on fragments from Lipari, albeit limited to pXRF investigations, allowed to enrich the knowledge on the Corinthian production exported to western areas as well as to discriminate, no longer based solely on autoptic observations and stylistic evaluations, between Corinthian productions and "local" imitations.
Endometrial carcinoma: use of tracer kinetic modeling of dynamic contrast-enhanced MRI for preoperative risk assessment
Authors: Ye Zhijun , Ning Gang , Li Xuesheng , Koh Tong San , Chen Huizhu , Bai Wanjing , Qu Haibo
Published: March 2022

Background

To compare two tracer kinetic models in predicting of preoperative risk types in endometrial carcinoma (EC) using DCE-MRI.

Methods

A prospective study of patients with EC was conducted with institutional ethics approval and written informed consent. DCE-MRI data was analyzed using the extended Tofts (ET) and the distributed parameter (DP) models. DCE parameters blood flow (F), mean transit time, blood volume (Vp), extravascular extracellular volume (Ve), permeability surface area product (PS), extraction fraction, transfer constant (Ktrans), and efflux rate (Kep) between high- and low-risk EC were compared using the Mann–Whitney test. Bland–Altman analysis was utilized to compare parameter consistency and Spearman test to assess parameter correlation. Diagnostic performance of DCE parameters was analyzed by receiver-operating characteristic curve and compared with traditional MRI assessment.

Results

Fifty-one patients comprised the study group. Patients with high-risk EC exhibited significantly lower Ktrans, Kep, F, Vp and PS (P < 0.001). ET-derived Ktrans and DP-derived F attained AUC of 0.92 and 0.91, respectively. Bland–Altman analysis showed that the consistency of Ve or Vp between the two models was low (P < 0.001) while Spearman test showed a strong correlation (r = 0.719, 0.871). Both Ktrans and F showed higher accuracy in predicting EC risk types than traditional MRI assessment.

Conclusions

Kinetic parameters derived from DCE-MRI revealed a more hypovascular microenvironment for high risk EC than to low- risk ones, providing potential imaging biomarkers in preoperative risk assessment that might improve individualized surgical planning and management of EC.
Firm bankruptcies and start-up activity in Switzerland during the COVID-19 crisis
Authors: Eckert Florian , Mikosch Heiner
Published: March 2022

This paper examines the incidence of firm bankruptcies and start-ups in Switzerland based on unique register data. We propose to assess the frequency of bankruptcies over time using the concept of excess mortality. During the COVID-19 crisis in 2020 and the first half of 2021, bankruptcy rates were substantially lower as compared to the pre-crisis period. This holds across most industries and regions. The Great Recession and the Swiss Franc Shock showed reverse patterns. Bankruptcies dropped more in industries and cantons, in which the share of firms who received a COVID-19 loan is comparatively high. In winter 2021, bankruptcies rebounded strongly. Since summer 2020, the number of new firm formations has been significantly higher compared to the time before the crisis. This is also in contrast to the previous crises. The strong start-up activity is driven by industries where the pandemic induced structural adjustments.
Numerical dispersion mitigation neural network for seismic modeling
Authors: Gadylshin Kirill , Vishnevsky Dmitry , Gadylshina Kseniia , Lisitsa Vadim
Published: March 2022

We have developed a novel approach for seismic modeling combining conventional finite differences with deep neural networks. The method includes the following steps. First, a training data set composed of a small number of common-shot gathers is generated. The data set is computed using a finite-difference scheme with fine spatial and temporal discretization. Second, the entire set of common-shot seismograms is generated using an inaccurate numerical method, such as a finite-difference scheme on a coarse mesh. Third, the numerical dispersion mitigation neural network is trained and applied to the entire data set to suppress the numerical dispersion. We have tested the approach on two 2D models, illustrating a significant acceleration of seismic modeling.
Dural Invasion as a Marker of Aggressive Pituitary Adenomas
Authors: Cooper Odelia , Bonert Vivien , Mamelak Adam N. , Bannykh Serguei , Melmed Shlomo
Published: March 2022

BACKGROUND:

Predictive markers of aggressive pituitary tumors have not been consistently demonstrated. Dural invasion and invasion-associated proteins, including matrix metalloproteinase-9 (MMP9) and cofilin, have been proposed to predict aggressive behavior and recurrence, but findings to date have been inconsistent.

OBJECTIVE:

To assess whether microscopic dural invasion predicts aggressive pituitary adenoma behavior and whether MMP9 and cofilin expression correlates with pathological and clinical invasion markers.

METHODS:

We retrospectively studied 328 consecutive pituitary mass resections by a single neurosurgeon at a single center; 254 were adenomas, and 98 had dural biopsies sent for routine pathological evaluation. Assessments included clinical features, postoperative course, and immunochemical expression of MMP9, cofilin, and phospho-cofilin. Recurrence was evaluated in those with at least 12 months of postoperative follow-up.

RESULTS:

Dural invasion was evident in 48% of biopsy specimens and was associated with male sex, larger tumors, suprasellar extension and sphenoid sinus invasion, cranial nerve palsies, and hypogonadism. Recurrence rates and the expression of MMP9, cofilin, and phospho-cofilin did not differ between those with and without dural invasion. However, differential expression of phospho-cofilin was associated with growth hormone deficiency and compressive pituitary mass effects.

CONCLUSION:

Dural invasion is associated with larger tumors, suprasellar and sphenoid sinus invasion, and pituitary failure but is not predictive of a more aggressive postoperative course. Routine dural biopsy is therefore of limited benefit in predicting postoperative recurrences. Cofilin expression may be an adjunctive biomarker of invasion in recurrent tumors, but MMP9 expression does not predict tumor behavior.
The topography of corticopontine projections is controlled by postmitotic expression of the area-mapping gene Nr2f1
Authors: Tocco Chiara , Øvsthus Martin , Bjaalie Jan G. , Leergaard Trygve B. , Studer Michèle
Published: March 2022

Axonal projections from layer V neurons of distinct neocortical areas are topographically organized into discrete clusters within the pontine nuclei during the establishment of voluntary movements. However, the molecular determinants controlling corticopontine connectivity are insufficiently understood. Here, we show that an intrinsic cortical genetic program driven by Nr2f1 graded expression is directly implicated in the organization of corticopontine topographic mapping. Transgenic mice lacking cortical expression of Nr2f1 and exhibiting areal organization defects were used as model systems to investigate the arrangement of corticopontine projections. By combining three-dimensional digital brain atlas tools, Cre-dependent mouse lines and axonal tracing, we show that Nr2f1 expression in postmitotic neurons spatially and temporally controls somatosensory topographic projections, whereas expression in progenitor cells influences the ratio between corticopontine and corticospinal fibres passing the pontine nuclei. We conclude that cortical gradients of area-patterning genes are directly implicated in the establishment of a topographic somatotopic mapping from the cortex onto pontine nuclei.
Effectiveness of Gatekeeper Training Program (GTP) on awareness, attitude, mental help seeking intention and gatekeeper behavior among Koraga tribe: A study protocol
Authors: Noronha Flavia Sharlet , Jose Tessy Treesa , George Anice , George Linu Sara
Published: March 2022

Aim: This study aims to build the capacity of the people at grass root level as gatekeepers of mental health. It will assess the effectiveness of the Gatekeeper Training Program (GTP) on gatekeeper behaviour, awareness, attitude, and mental help seeking intention.

Design: An evaluative research approach in two phases. Phase 1: Cross-sectional house-to-house exploratory survey. Phase 2: A quasi-experimental design with multiple follow ups at 0, 6 and 12 months.

Method: Data will be collected using standardized tools like Mental Health Knowledge Questionnaire (MHKQ), Community Attitude towards Mentally Ill (CAMIS), Mental Help Seeking Intention (MHSIS) and Gatekeeper Behavior Scale (GBS). For Phase 1, a house-to-house survey will be conducted among the selected colonies of Koraga tribe to determine their awareness, attitude, and mental help seeking intention regarding common mental health problems. Phase 2 includes identification of the leaders/representatives of the selected tribal colonies, and involving them in GTP. Pre-test and multiple post-test will be conducted in Phase 2 at 0, 6, 12 months.  The study is funded by Indian Council of Medical Research from 16 August 2021 for 3 years duration.

Discussion: Treatment gap in psychiatric disorders remains an issue of great concern. Evidence based research promotes task shifting approaches in dealing with mental health problems in the community. Capacity building programs like GTP for the underprivileged section of the society are important especially in low and middle income group of countries.

Impact: This need based GTP, will ensure mental health first aid in the society. Early identification of people with mental health problems at their doorsteps has huge impact on the prognosis of the illness, closing the treatment gap and stigma reduction.
The genome sequence of the chicken of the woods fungus, Laetiporus sulphureus (Bull.) Murrill, 1920
Authors: Wright Richard , Woof Kieran , Douglas Brian , Gaya Ester ,   Royal Botanic Gardens Kew Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: March 2022

We present a genome assembly from an individual Laetiporus sulphureus (the chicken of the woods fungus; Basidiomycota; Agaricomycetes; Polyporales; Laetiporaceae). The genome sequence is 37.4 megabases in span. The complete assembly is scaffolded into 14 chromosomal pseudomolecules.
Attention and Underreaction-Related Anomalies
Authors: Chen Xin , He Wei , Tao Libin , Yu Jianfeng
Published: March 2022

Recent studies have proposed a large set of powerful anomaly-based factors in the stock market. This study examines the role of investor inattention in the corresponding anomalies underlying these factors and other underreaction-related anomalies. Using media coverage as a proxy for investor attention, we show that the anomalies underlying many recently proposed prominent factors are much more pronounced among firms with low media coverage in portfolio-formation periods. In addition, we find many other prominent anomalies that previous literature has attributed to underreaction also tend to perform much better among firms with low media coverage. The average Fama-French five-factor alpha spread of these anomalies is about 0.97% per month among firms with low news coverage and only 0.24% per month among firms with high news coverage. Moreover, most of the alpha spread comes from the short leg of the anomalies and from the firms that are more difficult to arbitrage. Overall, our evidence indicates that investor inattention at least partially drives many of the recently proposed factors.

This paper was accepted by Haoxiang Zhu, finance.

Funding: L. Tao received financial support from the National Natural Science Foundation of China [Grant 72171050], the Ministry of Education Project of Humanities and Social Sciences [Grant No. 17YJCZH161], and the University of International Business and Economics Fund for Distinguished Young Scholars [Grant No. 18JQ07]. J. Yu acknowledges financial support from the National Natural Science Foundation of China [Grant No. 71790591].

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4332 .
Pooling Agents for Customer-Intensive Services
Authors: Wang Zhongbin , Yang Luyi , Cui Shiliang , Ülkü Sezer , Zhou Yong-Pin
Published: March 2022

To Pool or Not to Pool? Analyzing Customer-Intensive Services with Strategic Agents

In customer-intensive services where service quality increases with service time, service providers commonly pool their agents and give performance bonuses that reward agents for achieving greater customer satisfaction and serving more customers. Conventional wisdom suggests that pooling agents reduce customer wait time whereas performance bonuses motivate agents to produce high-quality services, both of which should boost customer satisfaction. However, in “Pooling Agents for Customer-Intensive Services,” Wang, Yang, Cui, Ülkü, and Zhou find that when agents act strategically, they may choose to speed up under pooling in an attempt to serve more customers, thus undermining service quality. If this happens, pooling can backfire and result in both lower customer satisfaction and agent payoff. Consequently, the researchers propose a simple practical solution to restore the efficiency of pooling. They propose pooling a portion of the performance bonuses (incentive pooling) in conjunction with pooling agents (operational pooling).
Awareness and use of prone position for awake patients with suspected COVID-19
Authors: Gander Bradley , Trestrail Nick , Pugh Kieren
Published: March 2022

Introduction:

Evidence is growing that prone positioning may be a simple, safe, and effective technique to improve oxygenation in awake patients with COVID-19 who are unresponsive to initial therapy. However, there is little evidence about its use in the prehospital environment. This study explores clinician awareness and experiences of this in a large ambulance service in south east England.

Methods:

An online survey was distributed to 3377 operational ambulance clinicians working for the South East Coast Ambulance Service NHS Foundation Trust to assess their awareness of using the prone position for patients with suspected COVID-19 and their experiences of its use in their practice.

Results:

A total of 278 respondents completed the survey, of whom 229 were aware of the use of the prone position for awake patients with COVID-19 and 18 had attempted to use it in their practice. Ten reported improvements in clinical observations and patient comfort, and six patients showed clinical improvement only. There were no reports of deterioration. The most common reason for not attempting prone positioning was the absence of formal training or guidance.

Conclusion:

Ambulance clinicians are aware of the use of the prone position for patients with COVID-19 and a small number have used it. The majority of clinicians who were aware of the procedure did not use it because of the lack of guidance or concerns over patient safety. When attempted, prone positioning in prehospital practice may be an example of practice borne of ‘clinical courage’. Further research is needed before the prone position can be routinely used in prehospital practice.
Diversity in practice
Authors: Costello Barry
Published: March 2022

As Barry Costello looks beyond his time as an NQP, he reflects on what's next…
Cognitive assessment and intervention in occupational therapy for Thai older adults with neurocognitive disorders
Authors:   Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai Province, Thailand, Chaiwong Pachpilai , Sungkarat Somporn ,   Department, of Physical Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai Province, Thailand, Rattakorn Phuanjai ,   Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai Province, Thailand, Munkhetvit Peeraya ,   Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai Province, Thailand
Published: March 2022

Background: Occupational therapists (OTs) have a significant role in maintaining clients' well-being. Understanding the current occupational therapy (OT) practice for the elderly with neurocognitive disorders (NCDs) brings effective service. Objectives: This study aimed to explore current OT practice for cognitive assessment and intervention for the elderly with NCDs in Thailand. Materials and methods: This study explored OT practices via questionnaire. Questionnaires were distributed to one hundred and ninety-one OTs throughout Thailand. Results: One hundred and fifty-two occupational therapists (79.87%) responded to the survey. Most worked full-time (94.08%), and 74.34% worked at general hospitals. Participants were more likely to employ standardized cognitive tests (45.33%) than non-standardized assessments (38.00%). Typical standardized tests were screening tests rather than comprehensive tests. The most reported cognitive problem was basic cognition (77.63% to 98.08%). The main cognitive intervention focused on basic cognition (80.92% to 94.74%). Typical interventions were caregiver education (83.89%), physical activity (73.15%), and perceptual retaining (68.46%). Challenges to OT intervention were therapists had poor evaluation skills, unclear intervention guidelines, and an insufficient number of therapists. Conclusion: OTs should participate in further education and develop a guideline and appropriate comprehensive cognitive assessment tools.
Ultraviolet C random lasing at 230–280 nm from Pr3+ doped bulk crystal resonators by two-photon absorption
Authors: Zhu Zheng , Wang Yin , Zhang Wenfei , Wu Tao , Wang Xiaofei , Yang Yanmin , Wang Ting , Xu Xuhui
Published: March 2022

Ultraviolet solid-state light sources, especially in the short-wave ultraviolet band, are attracting great attention for potential applications in high-density optical data storage, biomedical research, and water and air purification and sterilization. As one of the means to generate solid-state short-wavelength lasers, upconversion technology, which can transform a low-energy photon to a high-energy photon, has a simple structure and does not require strict phase-matching conditions. However, because of the high non-radiative decay rate during multiphoton absorption process, the short-wave upconversion ultraviolet lasing is still difficult to achieve. Here, under 450 nm blue laser excitation, we have successfully obtained ultraviolet C random lasing from a Pr3+ doped YPO4 single crystal via two-photon absorption. Presently, ultraviolet C random lasing with the wavelength range of 230–280 nm is the shortest wavelength for upconversion lasing emission.
A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease
Authors: Bérard Morgan , Sheta Razan , Malvaut Sarah , Rodriguez-Aller Raquel , Teixeira Maxime , Idi Walid , Turmel Roxanne , Alpaugh Melanie , Dubois Marilyn , Dahmene Manel , Salesse Charleen , Lamontagne-Proulx Jérôme , St-Pierre Marie-Kim , Tavassoly Omid , Luo Wen , Del Cid-Pellitero Esther , Qazi Raza , Jeong Jae-Woong , Durcan Thomas M. , Vallières Luc , Tremblay Marie-Eve , Soulet Denis , Lévesque Martin , Cicchetti Francesca , Fon Edward A. , Saghatelyan Armen , Oueslati Abid
Published: March 2022

Neurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, the exact role of protein aggregation in the pathophysiology of these disorders remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of protein aggregation, and the investigation of early dynamic events associated with inclusion formation. Here, we report on the development of a light-inducible protein aggregation (LIPA) system that enables spatiotemporal control of α-synuclein (α-syn) aggregation into insoluble deposits called Lewy bodies (LBs), the pathological hallmark of Parkinson disease (PD) and other proteinopathies. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical, and ultrastructural features of authentic LBs observed in PD-diseased brains. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration and PD-like motor impairments. Collectively, our findings provide a new tool for the generation, visualization, and dissection of the role of α-syn aggregation in PD.
Tumor cell intrinsic and extrinsic features predict prognosis in estrogen receptor positive breast cancer
Authors: Yao Kevin , Schaafsma Evelien , Zhang Baoyi , Cheng Chao
Published: March 2022

Although estrogen-receptor-positive (ER+) breast cancer is generally associated with favorable prognosis, clinical outcome varies substantially among patients. Genomic assays have been developed and applied to predict patient prognosis for personalized treatment. We hypothesize that the recurrence risk of ER+ breast cancer patients is determined by both genomic mutations intrinsic to tumor cells and extrinsic immunological features in the tumor microenvironment. Based on the Cancer Genome Atlas (TCGA) breast cancer data, we identified the 72 most common genomic aberrations (including gene mutations and indels) in ER+ breast cancer and defined sample-specific scores that systematically characterized the deregulated pathways intrinsic to tumor cells. To further consider tumor cell extrinsic features, we calculated immune infiltration scores for six major immune cell types. Many individual intrinsic features are predictive of patient prognosis in ER+ breast cancer, and some of them achieved comparable accuracy with the Oncotype DX assay. In addition, statistical learning models that integrated these features predicts the recurrence risk of patients with significantly better performance than the Oncotype DX assay (our optimized random forest model AUC = 0.841, Oncotype DX model AUC = 0.792, p = 0.04). As a proof-of-concept, our study indicates the great potential of genomic and immunological features in prognostic prediction for improving breast cancer precision medicine. The framework introduced in this work can be readily applied to other cancers.
The impact of the spatial heterogeneity of resistant cells and fibroblasts on treatment response
Authors: M A Masud , Kim Jae-Young , Pan Cheol-Ho , Kim Eunjung
Published: March 2022

A long-standing practice in the treatment of cancer is that of hitting hard with the maximum tolerated dose to eradicate tumors. This continuous therapy, however, selects for resistant cells, leading to the failure of the treatment. A different type of treatment strategy, adaptive therapy, has recently been shown to have a degree of success in both preclinical xenograft experiments and clinical trials. Adaptive therapy is used to maintain a tumor’s volume by exploiting the competition between drug-sensitive and drug-resistant cells with minimum effective drug doses or timed drug holidays. To further understand the role of competition in the outcomes of adaptive therapy, we developed a 2D on-lattice agent-based model. Our simulations show that the superiority of the adaptive strategy over continuous therapy depends on the local competition shaped by the spatial distribution of resistant cells. Intratumor competition can also be affected by fibroblasts, which produce microenvironmental factors that promote cancer cell growth. To this end, we simulated the impact of different fibroblast distributions on treatment outcomes. As a proof of principle, we focused on five types of distribution of fibroblasts characterized by different locations, shapes, and orientations of the fibroblast region with respect to the resistant cells. Our simulation shows that the spatial architecture of fibroblasts modulates tumor progression in both continuous and adaptive therapy. Finally, as a proof of concept, we simulated the outcomes of adaptive therapy of a virtual patient with four metastatic sites composed of different spatial distributions of fibroblasts and drug-resistant cell populations. Our simulation highlights the importance of undetected metastatic lesions on adaptive therapy outcomes.
Evolutionary insights into primate skeletal gene regulation using a comparative cell culture model
Authors: Housman Genevieve , Briscoe Emilie , Gilad Yoav
Published: March 2022

The evolution of complex skeletal traits in primates was likely influenced by both genetic and environmental factors. Because skeletal tissues are notoriously challenging to study using functional genomic approaches, they remain poorly characterized even in humans, let alone across multiple species. The challenges involved in obtaining functional genomic data from the skeleton, combined with the difficulty of obtaining such tissues from nonhuman apes, motivated us to consider an alternativein vitrosystem with which to comparatively study gene regulation in skeletal cell types. Specifically, we differentiated six human (Homo sapiens) and six chimpanzee (Pan troglodytes) induced pluripotent stem cell lines (iPSCs) into mesenchymal stem cells (MSCs) and subsequently into osteogenic cells (bone cells). We validated differentiation using standard methods and collected single-cell RNA sequencing data from over 100,000 cells across multiple samples and replicates at each stage of differentiation. While most genes that we examined display conserved patterns of expression across species, hundreds of genes are differentially expressed (DE) between humans and chimpanzees within and across stages of osteogenic differentiation. Some of these interspecific DE genes show functional enrichments relevant in skeletal tissue trait development. Moreover, topic modeling indicates that interspecific gene programs become more pronounced as cells mature. Overall, we propose that thisin vitromodel can be used to identify interspecific regulatory differences that may have contributed to skeletal trait differences between species.
The nitrate-inducible NAC transcription factor NAC056 controls nitrate assimilation and promotes lateral root growth in Arabidopsis thaliana
Authors: Xu Peipei , Ma Wei , Hu Jinbo , Cai Weiming
Published: March 2022

Nitrate can affect many aspects of plant growth and development, such as promoting root growth and inhibiting the synthesis of secondary metabolites. However, the mechanisms underlying such effects and how plants can integrate nitrate signals and root growth needs further exploration. Here, we identified a nitrate-inducible NAC family transcription factor (TF) NAC056 which promoted both nitrate assimilation and root growth in Arabidopsis. NAC056 is a nuclear-localized transcription activator, which is predominantly expressed in the root system and hypocotyl. Using the yeast one-hybrid assay, we identified the NAC056-specific binding sequence (NAC56BM), T [T/G/A] NCTTG. We further showed that the nac056 mutant compromised root growth. NAC056 overexpression promotes LR Initiation and nitrate deficiency tolerance. Using RNA sequencing analysis and in vitro biochemical experiment, we found NAC056 regulated the expression of genes required for NO3− assimilation, directly targeting the key nitrate assimilation gene NIA1. In addition, mutation of NIA1 suppresses LR development and nitrate deficiency tolerance in the 35S::NAC056 transgenic plants. Therefore, NAC056 mediates the response of plants to environmental nitrate signals to promote root growth in Arabidopsis.
The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time
Authors: Fox Alisa , Marino Jessica , Amanat Fatima , Oguntuyo Kasopefoluwa Y. , Hahn-Holbrook Jennifer , Lee Benhur , Zolla-Pazner Susan , Powell Rebecca L.
Published: March 2022

Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have reported on the presence of SARS-CoV-2-specific antibodies in human milk. We now report the prevalence of SARS-CoV-2 IgA in the milk of 74 COVID-19-recovered participants, and find that 89% of samples are positive for Spike-specific IgA. In a subset of these samples, 95% exhibited robust IgA activity as determined by endpoint binding titer, with 50% considered high-titer. These IgA-positive samples were also positive for Spike-specific secretory antibody. Levels of IgA antibodies and secretory antibodies were shown to be strongly positively correlated. The secretory IgA response was dominant among the milk samples tested compared to the IgG response, which was present in 75% of samples and found to be of high-titer in only 13% of cases. Our IgA durability analysis using 28 paired samples, obtained 4–6 weeks and 4–10 months after infection, found that all samples exhibited persistently significant Spike-specific IgA, with 43% of donors exhibiting increasing IgA titers over time. Finally, COVID-19 and pre-pandemic control milk samples were tested for the presence of neutralizing antibodies; 6 of 8 COVID-19 samples exhibited neutralization of Spike-pseudotyped VSV (IC50range, 2.39–89.4ug/mL) compared to 1 of 8 controls. IgA binding and neutralization capacities were found to be strongly positively correlated. These data are highly relevant to public health, not only in terms of the protective capacity of these antibodies for breastfed infants, but also for the potential use of such antibodies as a COVID-19 therapeutic, given that secretory IgA is highly in all mucosal compartments.
A calming hug: Design and validation of a tactile aid to ease anxiety
Authors: Haynes Alice C. , Lywood Annie , Crowe Emily M. , Fielding Jessica L. , Rossiter Jonathan M. , Kent Christopher
Published: March 2022

Anxiety disorders affect approximately one third of people during their lifetimes and are the ninth leading cause of global disability. Current treatments focus on therapy and pharmacological interventions. However, therapy is costly and pharmacological interventions often have undesirable side-effects. Healthy people also regularly suffer periods of anxiety. Therefore, a non-pharmacological, intuitive, home intervention would be complementary to other treatments and beneficial for non-clinical groups. Existing at-home anxiety aids, such as guided meditations, typically employ visual and/or audio stimuli to guide the user into a calmer state. However, the tactile sense has the potential to be a more natural modality to target in an anxiety-calming device. The tactile domain is relatively under-explored, but we suggest that there are manifold physiological and affective qualities of touch that lend it to the task. In this study we demonstrate that haptic technology can offer an enjoyable, effective and widely accessible alternative for easing state anxiety. We describe a novel huggable haptic interface that pneumatically simulates slow breathing. We discuss the development of this interface through a focus group evaluating five prototypes with embedded behaviours (‘breathing’, ‘purring’, ‘heartbeat’ and ‘illumination’). Ratings indicated that the ‘breathing’ prototype was most pleasant to interact with and participants described this prototype as ‘calming’ and ‘soothing’, reminding them of a person breathing. This prototype was developed into an ergonomic huggable cushion containing a pneumatic chamber powered by an external pump allowing the cushion to ‘breathe’. A mixed-design experiment (n = 129) inducing anxiety through a group mathematics test found that the device was effective at reducing pre-test anxiety compared to a control (no intervention) condition and that this reduction in anxiety was indistinguishable from that of a guided meditation. Our findings highlight the efficacy of this interface, demonstrating that haptic technologies can be effective at easing anxiety. We suggest that the field should be explored in more depth to capture the nuances of different modalities in relation to specific situations and trait characteristics.
Coronavirus Resistance Database (CoV-RDB): SARS-CoV-2 susceptibility to monoclonal antibodies, convalescent plasma, and plasma from vaccinated persons
Authors: Tzou Philip L. , Tao Kaiming , Pond Sergei L. Kosakovsky , Shafer Robert W.
Published: March 2022

As novel SARS-CoV-2 variants with different patterns of spike protein mutations have emerged, the susceptibility of these variants to neutralization by antibodies has been rapidly assessed. However, neutralization data are generated using different approaches and are scattered across different publications making it difficult for these data to be located and synthesized. The Stanford Coronavirus Resistance Database (CoV-RDB; https://covdb.stanford.edu) is designed to house comprehensively curated published data on the neutralizing susceptibility of SARS-CoV-2 variants and spike mutations to monoclonal antibodies (mAbs), convalescent plasma (CP), and vaccinee plasma (VP). As of December 31, 2021, CoV-RDB encompassed 257 publications including 91 (35%) containing 9,070 neutralizing mAb susceptibility results, 131 (51%) containing 16,773 neutralizing CP susceptibility results, and 178 (69%) containing 33,540 neutralizing VP results. The database also records which spike mutations are selected during in vitro passage of SARS-CoV-2 in the presence of mAbs and which emerge in persons receiving mAbs as treatment. The CoV-RDB interface interactively displays neutralizing susceptibility data at different levels of granularity by filtering and/or aggregating query results according to one or more experimental conditions. The CoV-RDB website provides a companion sequence analysis program that outputs information about mutations present in a submitted sequence and that also assists users in determining the appropriate mutation-detection thresholds for identifying non-consensus amino acids. The most recent data underlying the CoV-RDB can be downloaded in its entirety from a GitHub repository in a documented machine-readable format.
External childcare and socio-behavioral development in Switzerland: Long-term relations from childhood into young adulthood
Authors: Averdijk Margit , Ribeaud Denis , Eisner Manuel
Published: March 2022

This study examined early external childcare in relation to development from age 7 to 20. A Swiss sample was used (N= 1,225; 52% male). Development included multi-informant-reported externalizing behavior, internalizing problems, prosocial behavior, delinquency, and substance use. Growth curve models revealed that, dependent on the informant, time in a daycare center was related to increased externalizing and internalizing problems until at least age 11. It was not related to delinquency. Roughly three days per week at a daycare mother or playgroup was related to increased externalizing behavior. External family care was associated with increased prosocial behavior. Finally, time in a daycare center was associated with fewer externalizing but more internalizing problems and substance use for children from vulnerable backgrounds. This relation with substance use lasted to age 20.
The economic impact of organic production in Brazil: A study based on municipal production hotspots
Authors: Vogt Camila de Moura , Alcantara Alencar Douglas , Fochezatto Adelar
Published: March 2022

The agroecological products market has increased substantially worldwide in recent decades. As a traditional agricultural country, Brazil has followed this trend and has increased the production of certified organic products in recent years. In addition, the country is one of the largest consumer markets in Latin America. This study aims to measure the effects of organic production on the economic development of municipalities through spatial analysis and econometric methodologies. Thus, it estimates the impact of organic production hotspots on the 2017 gross domestic product of Brazilian municipalities and the agriculture gross value added. The results indicate that the organic hotspots had a positive effect on both variables. Therefore, the results corroborate incentives for organic production as an alternative for the sustainable development of the agricultural sector.
Time to start of tuberculosis treatment in penitentiary system of Kyrgyz Republic: A retrospective cohort study
Authors: Soltobekova Nazgul , Kozukeev Turatbek , Yiehdego Ghirmai , Labib Fatah , Hovhannesyan Arax , Rossi Rodolfo
Published: March 2022

Background

Tuberculosis burden among the incarcerated population is generally higher than that of general population. Early diagnosis and prompt initiation of treatment are key strategies to contain disease transmission. The aim of this study was to determine the time to treatment initiation among inmates with new smear or Xpert MTB/RIF positive pulmonary tuberculosis and explore risk factors associated with delayed treatment initiation in prison settings.

Methods

We conducted a retrospective cohort study using routine health care data from prison settings in Kzrgyz Republic on new pulmonary tuberculosis patients confirmed by smear microscopy or GeneXpert MTB/RIF during 2014–2019. We computed delay in start of treatment—days from specimen collection to treatment initiation—for exposure variables. We dichotomized treatment delay using 10-day cut-off point,and used logistic regression to identify factors associated with treatment delay.

Results

Among 406 cases included into analysis, the median delay to treatment initiation was 7 days [IQR: 2–16 days]. Using 10-day cut-off, 189 (46.6%) patients had delayed treatment initiation. Treatment delay was negatively associated with smear positivity [adjusted OR (aOR) = 0.44, 95% CI 0.29–0.68] compared to smear negative patients, while patients with isoniazid resistant (aOR = 2.61, 95%CI 1.49–4.56) and rifampicin resistant tuberculosis (aOR = 4.14, 95%CI 2.56–6.77) had increased delay compared to patients who were sensitive for both rifampicin and isoniazid.

Conclusion

Timely diagnosis and effective treatment remain the cornerstone of TB control program populations in the general and in prison settings in particular. Prison authorities need to address all potential areas of delay in TB diagnosis and treatment to strengthen their TB control efforts so that prisons remain free of TB for detainees, prison staff and visitors. These include improved supply of TB drugs, early detection of TB cases and improved collaboration with the health authorities outside the prison system.
Development of a detailed canine gait analysis method for evaluating harnesses: A pilot study
Authors: Pálya Zsófia , Rácz Kristóf , Nagymáté Gergely , Kiss Rita M.
Published: March 2022

Dog harnesses are becoming more popular, with their large variety stemming from the idea that different dogs and scenarios require different types of harnesses. While their benefits over collars are self-explanatory, there is a lack of research on their effect on gait, and even the existing studies examine only a limited set of parameters. The goal of present study was to establish a method capable of quantifying canine gait in detail. Based on 3D motion capture, the developed method allows for the examination of 18 joint angles and 35 spatio-temporal parameters throughout multiple gait cycles, and can be used to analyze canine movement in detail in any kind of scenario (e.g. comparing healthy and lame dogs, or measuring the effect of training). The method is presented through the measurement of how different harnesses affect walking kinematics compared to free (unleashed) movements. Four dogs with varying body sizes and breeds and multiple types of harnesses were included. Marker data was filtered using a zero-lag 6th order Butterworth-filter with a cutoff frequency of 20 Hz. The normality of the spatio-temporal and joint range of motion parameters was tested using the Anderson-Darling test (p = 0.05), with most parameters passing in 60+% of test cases. Swing time and range of motion of the sagittal aspect of spinal angle at T1 vertebrae failed more regularly, both resulting from the measurement setup rather than the actual parameters being not normally distributed. Two-sample Kolmogorov-Smirnov tests (p = 0.05) were used to compare each parameter’s distribution between cases, showing that most parameters are significantly altered by the harnesses in about 2/3rd of the cases. Based on the results, there’s no absolute superior harness, however, it is possible to select the best fit for a specific dog and application, justifying their large variety.