bluuebunny/crossref_metadata_2025_split huggingface dataset:
The introduction of a regional Norwegian HEMS coordinator: an assessment of the effects on response times, geographical service areas and severity scores
Authors: Ulvin Ole Erik , Skjærseth Eivinn Årdal , Haugland Helge , Thorsen Kjetil , Nordseth Trond , Orre Marie Falch , Vesterhus Lars , Krüger Andreas Jørstad 
Published: August 2022

Abstract
Background
Due to unwanted delays and suboptimal resource control of helicopter emergency medical services (HEMS), regional HEMS coordinators have recently been introduced in Norway. This may represent an unnecessary link in the alarm chain, which could cause delays in HEMS dispatch. Systematic evaluations of this intervention are lacking. We wanted to conduct this study to assess possible changes in HEMS response times, mission distribution patterns and patient characteristics within our region following this intervention.

Methods
We retrospectively collected timeline parameters, patient characteristics and GPS positions from HEMS missions executed by three regional HEMS bases in Mid-Norway during 2017–2018 (preintervention) and 2019 (postintervention). The mean regional response time in HEMS missions was assessed by an interrupted time series analysis (ITS). The geographical mission distribution between regional HEMS resources was assessed by a before-after study with a convex hull-based method.

Results
There was no significant change in the level (-0.13 min/month, p = 0.88) or slope (-0.13 min/month, p = 0.30) of the mean regional response time trend line pre- and postintervention. For one HEMS base, the service area was increased, and the median mission distance was significantly longer. For the two other bases, the service areas were reduced. Both the mean NACA score (4.13 ± SD 0.027 vs 3.98 ± SD 0.04, p < 0.01) and the proportion of patients with severe illness or injury (NACA 4–7, 68.2% vs 61.5%, p < 0.001) were higher in the postintervention group.

Conclusion
The introduction of a regional HEMS coordinator in Mid-Norway did not cause prolonged response times in acute HEMS missions during the first year after implementation. Higher NACA scores in the patients treated postintervention suggest better selection of HEMS use.
Use of hospitals in the New York City Metropolitan Region, by race: how separate? How equal in resources and quality?
Authors: Liu Bian , Ornstein Katherine A. , Frydman Julia L. , Kelley Amy S. , Benn Emma K. T. , Siu Albert L. 
Published: August 2022

Abstract
Background
Although racial and ethnic minorities disproportionately use some hospitals, hospital-based racial and ethnic composition relative to geographic region and its association with quality indicators has not been systematically analyzed.

Methods
We used four race and ethnicity categories: non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and Asian/Pacific Islander/Alaskan Native/American Indian (API/AIAN), as well as a combined non-NHW category, from the 2010 (latest year publicly available) Medicare Institutional Provider & Beneficiary Summary public use file for 84 hospitals in the New York City region. We assessed the relative distribution of race and ethnicity across hospitals grouped at different geographic levels (region, county, hospital referral region [HRR], or hospital service areas [HSA]) using the dissimilarity index. Hospital characteristics included quality star ratings, essential professional services and diagnostic/treatment equipment, bed size, total expenses, and patients with dual Medicare and Medicaid enrollment. We assessed Spearman’s rank correlation between hospital-based racial and ethnic composition and quality/structural measures.

Results
Dissimilarity Index decreases from region (range 30.3–40.1%) to county (range 13.7–23.5%), HRR (range 10.5–27.5%), and HSA (range 12.0–16.9%) levels. Hospitals with larger non-NHW patients tended to have lower hospital ratings and higher proportions of dually-enrolled patients. They were also more likely to be safety net hospitals and non-federal governmental hospitals.

Conclusions
In the NYC metropolitan region, there is considerable hospital-based racial and ethnic segregation of Medicare patients among non-NHW populations, extending previous research limited to NHB. Availability of data on racial and ethnic composition of hospitals should be made publicly available for researchers and consumers.
Assessing the time use and payments of multipurpose community health workers for the various roles they play—a quantitative study of the Mitanin programme in India
Authors: Garg Samir , Dewangan Mukesh , Nanda Prabodh , C Krishnendhu , Sahu Ashu , Xalxo Lalita 
Published: August 2022

Abstract
Background
Community health workers (CHWs) are crucial human resources for health. While specialist CHWs focus on a single disease vertically, the generalist or multipurpose CHWs perform wider functions. The current study was aimed at examining the time multipurpose CHWs spend on performing their different roles. This can help in understanding the importance they attach to each role. Since CHWs in many developing countries are classified as part-time volunteers, this study also aimed to assess the adequacy of CHW payments in relation to their time use.

Methods
The study covered a well-established CHW programme in India's Chhattisgarh state. It had 71,000 multipurpose part-time CHWs known as Mitanins. Data collection involved interviews with a representative sample of 660 rural and 406 urban Mitanins. A semi-structured tool was designed and field tested. It included 26 pre-coded activities of CHWs placed under their six purposes or roles. Prompting and triangulation were used during interviews to mitigate the possibility of over-reporting of work by CHWs. The recall period was of one week. Descriptive analysis included comparison of key indicators for rural and urban Mitanins. A multi-variate linear model was used to find the determinants of CHW time-use.

Results
The rural and urban Mitanins respectively spent 25.3 and 34.8 h per week on their CHW work. Apart from location (urban), the total time spent was associated with size of population covered. The time-use was well balanced between roles of service-linkage, providing health education and curative care directly, COVID-19 related work and action on social determinants of health. More than half of their time-use was for unpaid tasks. Most of the cash-incentives were concentrated on service linkage role. The average payment earned by Mitanins was less than 60% of legal minimum wage.

Conclusion
The time-use pattern of Mitanins was not dictated by cash-incentives and their solidarity with community seemed be a key motivator. To allow wide ranging CHW action like Mitanins, the population per CHW should be decided appropriately. The considerable time multipurpose CHWs spend on their work necessitates that developing countries develop policies to comply with World Health Organisation's recommendation to pay them fairly.
Age-specific difference in the association between prediabetes and subclinical atherosclerosis: an analysis of a chinese prospective cohort study
Authors: Cao Qiuyu , Xin Zhuojun , He Ruixin , Wang Tiange , Xu Min , Lu Jieli , Dai Meng , Zhang Di , Chen Yuhong , Zhao Zhiyun , Wang Shuangyuan , Lin Hong , Wang Weiqing , Ning Guang , Bi Yufang , Xu Yu , Li Mian 
Published: August 2022

Abstract
Background
Prediabetes is an important risk factor of cardiovascular disease (CVD) and is associated with subclinical atherosclerosis. However, the evidence of prediabetes as a cardiovascular risk factor is mainly derived from middle-aged adults. Recently, multiple studies supported that prediabetes in older adults would not lead to higher risk of CVD or mortality. We aimed to investigate the age-specific difference in the association between prediabetes and subclinical atherosclerosis in a Chinese prospective cohort study.

Methods
We included 4739 individuals aged ≥ 40 years and without diagnosed diabetes or CVD history, and divided them into middle-aged adults (age < 60) and older adults (age ≥ 60). Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2 h-PPG) and glycated hemoglobin (HbA1c) were measured at baseline to identify prediabetes status. At follow-up visits, subclinical atherosclerosis status was assessed by branchial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (CIMT). Logistic regression analysis, restricted cubic splines and cross-lagged path analysis were used in statistical analysis.

Results
1634 participants aged over 60 years, and 64.3% of them had prediabetes. 3105 participants aged 40–59 years, and 49.3% of them had prediabetes. We found that prediabetes was associated with increased risk of subclinical atherosclerosis in middle-aged adults, but the association attenuated substantially in older adults. Impaired glucose tolerance (IGT), compared to normal glucose tolerance, was associated with 39% lower risk of increased baPWV only in older adults. In accordance, the association between 2 h-PPG and risk of increased baPWV was “U-shaped” in older adults, while risk of elevated baPWV increased linearly with 2 h-PPG in middle-aged adults. In the cross-lagged analysis, increase in FPG and 2 h-PPG tended not to precede increase in baPWV in older adults, but appeared to increase simultaneously with baPWV in middle-aged ones.

Conclusion
Our results indicated that prediabetes might be less related to subclinical atherosclerosis in older adults than in middle-aged adults and suggested that age was important to consider in the care of adults with prediabetes.
Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis
Authors: Sugimoto Mitsuru , Suzuki Rei , Nozawa Yoshihiro , Takagi Tadayuki , Konno Naoki , Asama Hiroyuki , Sato Yuki , Irie Hiroki , Nakamura Jun , Takasumi Mika , Hashimoto Minami , Kato Tsunetaka , Kobashi Ryoichiro , Suzuki Osamu , Hashimoto Yuko , Hikichi Takuto , Ohira Hiromasa 
Published: August 2022

Abstract
Background
Biliary tract cancer (BTC) has a poor prognosis; therefore, useful biomarkers and treatments are needed. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-β superfamily, are elevated in patients with pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. Therefore, we investigated the effect of MIC-1 on BTC and assessed whether MIC-1 is a biomarker of or therapeutic target for BTC.

Methods
MIC-1 expression in BTC cells was determined by performing histological immunostaining, tissue microarray (TMA), western blotting, and reverse transcription PCR (RT–PCR). Cell culture experiments were performed to investigate the effect of MIC-1 on BTC cell lines (HuCCT-1 and TFK-1). The relationships between serum MIC-1 levels and either the disease state or the serum level of the apoptosis marker M30 were retrospectively verified in 118 patients with pancreaticobiliary disease (individuals with benign disease served as a control group, n = 62; BTC, n = 56). The most efficient diagnostic marker for BTC was also investigated.

Results
MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined using TMA, western blotting and RT–PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In serum analyses, serum MIC-1 levels showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved using the combination of MIC-1 and M30. The overall survival was significantly longer in BTC patients with serum MIC-1 < the median than in BTC patients with serum MIC-1 ≥ the median.

Conclusions
MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential therapeutic target for BTC.
Molecular characterization and genotype distribution of thioester-containing protein 1 gene in Anopheles gambiae mosquitoes in western Kenya
Authors: Onyango Shirley A. , Ochwedo Kevin O. , Machani Maxwell G. , Olumeh Julius O. , Debrah Isaiah , Omondi Collince J. , Ogolla Sidney O. , Lee Ming-Chieh , Zhou Guofa , Kokwaro Elizabeth , Kazura James W. , Afrane Yaw A. , Githeko Andrew K. , Zhong Daibin , Yan Guiyun 
Published: August 2022

Abstract
Background
Evolutionary pressures lead to the selection of efficient malaria vectors either resistant or susceptible to Plasmodium parasites. These forces may favour the introduction of species genotypes that adapt to new breeding habitats, potentially having an impact on malaria transmission. Thioester-containing protein 1 (TEP1) of Anopheles gambiae complex plays an important role in innate immune defenses against parasites. This study aims to characterize the distribution pattern of TEP1 polymorphisms among populations of An. gambiae sensu lato (s.l.) in western Kenya.

Methods
Anopheles gambiae adult and larvae were collected using pyrethrum spray catches (PSC) and plastic dippers respectively from Homa Bay, Kakamega, Bungoma, and Kisumu counties between 2017 and 2020. Collected adults and larvae reared to the adult stage were morphologically identified and then identified to sibling species by PCR. TEP1 alleles were determined in 627 anopheles mosquitoes using restriction fragment length polymorphisms-polymerase chain reaction (RFLP-PCR) and to validate the TEP1 genotyping results, a representative sample of the alleles was sequenced.

Results
Two TEP1 alleles (TEP1*S1 and TEP1*R2) and three corresponding genotypes (*S1/S1, *R2/S1, and *R2/R2) were identified. TEP1*S1 and TEP1*R2 with their corresponding genotypes, homozygous *S1/S1 and heterozygous *R2/S1 were widely distributed across all sites with allele frequencies of approximately 80% and 20%, respectively both in Anopheles gambiae and Anopheles arabiensis. There was no significant difference detected among the populations and between the two mosquito species in TEP1 allele frequency and genotype frequency. The overall low levels in population structure (FST = 0.019) across all sites corresponded to an effective migration index (Nm = 12.571) and low Nei’s genetic distance values (< 0.500) among the subpopulation. The comparative fixation index values revealed minimal genetic differentiation between species and high levels of gene flow among populations.

Conclusion
Genotyping TEP1 has identified two common TEP1 alleles (TEP1*S1 and TEP1*R2) and three corresponding genotypes (*S1/S1, *R2/S1, and *R2/R2) in An. gambiae s.l. The TEP1 allele genetic diversity and population structure are low in western Kenya.
Primary colonic melanoma: a rare entity
Authors: Xie Junhua , Dai Gang , Wu Yuhao 
Published: August 2022

AbstractGastrointestinal melanoma is usually metastatic in origin, and primary melanoma within the gastrointestinal tract is rarely reported. Colon is considered to be an extremely uncommon site for primary melanomas. Herein, we report the first case of a large primary melanoma within the transverse colon with gastric involvement. CT scan found a mass within the colon, which seemed to connect to the gastric antrum. Esophagogastroscopy showed an ulcerated lesion in the greater curvature of the stomach. Subsequent colonoscopy identified a large ulcerated lesion rendering significant stenosis of the transverse colon. Biopsy following colonoscopy indicated a diagnosis of colonic melanoma based on pathological findings, which identified submucosal malignant melanoma cells with epithelioid and spindle features. Immunohistochemical stains were positive for S-100, HMB-45, Vimentin, and Melan-A. A series of clinical and imaging examinations revealed no suspicious primary cutaneous or ocular lesions. The diagnosis of primary colonic melanoma was considered. A radical transverse colectomy with subtotal gastrectomy were conducted subsequently. Definite diagnosis of primary colonic melanoma can be established after ruling out the possibility of being a metastasis from other more common primary sites. Primary colonic melanomas are a challenge to diagnose and often need a multidisciplinary treatment approach, including surgery, BRAF-targeted therapy, and immunotherapy.
The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells
Authors: Martins Thaise S. , Fonseca Bruno M. , Rebelo Irene 
Published: August 2022

Abstract
Background
Inflammatory state within the ovaries can disrupt normal follicular dynamics, leading to reduced oocyte quality and infertility. How the production of inflammatory mediators generated by macrophages with different gene expression profile (M1 and M2) might activate inflammatory pathways, such as cyclooxygenase-2 (COX-2) and 5-, 12-, and 15-lipoxygenase (LOX), in human granulosa cells (hGCs) remains unclear.

Methods
In this study, we evaluated how M1 and M2 macrophages found in the ovaries affect the functions of hGCs isolated from women undergoing assisted reproductive technology (ART) and human ovarian granulosa COV434 cells. For this purpose, a model of interaction between hGCs and COV434 cells and conditioned media (CMs) obtained from culture of M0, M1 and M2 macrophages was established. We used real-time PCR and western blotting to detect the expression of COX-2 and 5-, 12-, and 15-LOX as biomarkers of oocyte competence.

Results
Our data showed that M2 macrophages with anti-inflammatory characteristics were able to significantly increase the expression of COX-2 in hGCs. We also demonstrated that M1 macrophages with pro-inflammatory characteristics were able to significantly increase the expression of 12-LOX in hGCs. However, there was no observed expression of 5-LOX and no significant alteration in the expression of 15-LOX in hGCs. Regarding COV434 cells, we found that CM from M2 macrophage resulted in an increase in COX-2, 5-LOX and 15-LOX mRNA and protein levels. No expression of 12-LOX by COV434 cells was observed when exposed to CMs from M1 and M2 macrophages.

Conclusions
Our research indicated that the production of pro-resolving mediators by hGCs can, at least in part, reverse the physiological inflammation present in the ovaries.
Androgen receptor variant-7 regulation by tenascin-c induced src activation
Authors: Thomas Rintu , Jerome John Michael , Dang Truong D. , Souto Eric P. , Mallam Joshua N. , Rowley David R. 
Published: August 2022

Abstract
Background
Bone metastatic prostate cancer does not completely respond to androgen-targeted therapy and generally evolves into lethal castration resistant prostate cancer (CRPC). Expression of AR-V7- a constitutively active, ligand independent splice variant of AR is one of the critical resistant mechanisms regulating metastatic CRPC. TNC is an extracellular matrix glycoprotein, crucial for prostate cancer progression, and associated with prostate cancer bone metastases. In this study, we investigated the mechanisms that regulate AR-V7 expression in prostate cancer cells interacting with osteogenic microenvironment including TNC.

Methods
Prostate cancer/preosteoblast heterotypical organoids were evaluated via immunofluorescence imaging and gene expression analysis using RT-qPCR to assess cellular compartmentalization, TNC localization, and to investigate regulation of AR-V7 in prostate cancer cells by preosteoblasts and hormone or antiandrogen action. Prostate cancer cells cultured on TNC were assessed using RT-qPCR, Western blotting, cycloheximide chase assay, and immunofluorescence imaging to evaluate (1) regulation of AR-V7, and (2) signaling pathways activated by TNC. Identified signaling pathway induced by TNC was targeted using siRNA and a small molecular inhibitor to investigate the role of TNC-induced signaling activation in regulation of AR-V7. Both AR-V7- and TNC-induced signaling effectors were targeted using siRNA, and TNC expression assessed to evaluate potential feedback regulation.

Results
Utilizing heterotypical organoids, we show that TNC is an integral component of prostate cancer interaction with preosteoblasts. Interaction with preosteoblasts upregulated both TNC and AR-V7 expression in prostate cancer cells which was suppressed by testosterone but elevated by antiandrogen enzalutamide. Interestingly, the results demonstrate that TNC-induced Src activation regulated AR-V7 expression, post-translational stability, and nuclear localization in prostate cancer cells. Treatment with TNC neutralizing antibody, Src knockdown, and inhibition of Src kinase activity repressed AR-V7 transcript and protein. Reciprocally, both activated Src and AR-V7 were observed to upregulate autocrine TNC gene expression in prostate cancer cells.

Conclusion
Overall, the findings reveal that prostate cancer cell interactions with the cellular and ECM components in the osteogenic microenvironment plays critical role in regulating AR-V7 associated with metastatic CRPC.
CRISPR/Cas9 genome editing to create nonhuman primate models for studying stem cell therapies for HIV infection
Authors: Schmidt Jenna Kropp , Reynolds Matthew R. , Golos Thaddeus G. , Slukvin Igor I. 
Published: August 2022

AbstractNonhuman primates (NHPs) are well-established basic and translational research models for human immunodeficiency virus (HIV) infections and pathophysiology, hematopoietic stem cell (HSC) transplantation, and assisted reproductive technologies. Recent advances in CRISPR/Cas9 gene editing technologies present opportunities to refine NHP HIV models for investigating genetic factors that affect HIV replication and designing cellular therapies that exploit genetic barriers to HIV infections, including engineering mutations into CCR5 and conferring resistance to HIV/simian immunodeficiency virus (SIV) infections. In this report, we provide an overview of recent advances and challenges in gene editing NHP embryos and discuss the value of genetically engineered animal models for developing novel stem cell-based therapies for curing HIV.
Upper limb soft robotic wearable devices: a systematic review
Authors: Bardi Elena , Gandolla Marta , Braghin Francesco , Resta Ferruccio , Pedrocchi Alessandra L. G. , Ambrosini Emilia 
Published: August 2022

AbstractIntroductionSoft robotic wearable devices, referred to as exosuits, can be a valid alternative to rigid exoskeletons when it comes to daily upper limb support. Indeed, their inherent flexibility improves comfort, usability, and portability while not constraining the user’s natural degrees of freedom. This review is meant to guide the reader in understanding the current approaches across all design and production steps that might be exploited when developing an upper limb robotic exosuit.MethodsThe literature research regarding such devices was conducted in PubMed, Scopus, and Web of Science. The investigated features are the intended scenario, type of actuation, supported degrees of freedom, low-level control, high-level control with a focus on intention detection, technology readiness level, and type of experiments conducted to evaluate the device.ResultsA total of 105 articles were collected, describing 69 different devices. Devices were grouped according to their actuation type. More than 80% of devices are meant either for rehabilitation, assistance, or both. The most exploited actuation types are pneumatic (52%) and DC motors with cable transmission (29%). Most devices actuate 1 (56%) or 2 (28%) degrees of freedom, and the most targeted joints are the elbow and the shoulder. Intention detection strategies are implemented in 33% of the suits and include the use of switches and buttons, IMUs, stretch and bending sensors, EMG and EEG measurements. Most devices (75%) score a technology readiness level of 4 or 5.ConclusionAlthough few devices can be considered ready to reach the market, exosuits show very high potential for the assistance of daily activities. Clinical trials exploiting shared evaluation metrics are needed to assess the effectiveness of upper limb exosuits on target users.