bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol for an efficacy trial of the “PrEP for Health” intervention to increase HIV PrEP use among people who inject drugs
Authors: Bazzi Angela R. , Bordeu Michelle , Baumgartner Katrina , Sproesser Darien M. , Bositis Christopher M. , Krakower Douglas S. , Mimiaga Matthew J. , Biello Katie B.
Published: March 2023

Background

HIV incidence has recently increased among people who inject drugs (PWID) across the United States, with outbreaks occurring in states with long-standing syringe service programs (SSPs) including Massachusetts (MA). Antiretroviral pre-exposure prophylaxis (PrEP) is an evidence-based HIV prevention strategy recommended for PWID, but uptake in this marginalized population is extraordinarily low.

Methods

We describe the design and procedures for a National Institute on Drug Abuse (NIDA)-funded (R01) randomized controlled trial (RCT) testing the efficacy of “PrEP for Health,” a multicomponent behavioral intervention to increase PrEP uptake, adherence, and persistence among HIV-negative PWID attending SSPs in two areas of the U.S. Northeast that are heavily affected by injection-related HIV transmission. Participants are equally randomized to receive the “PrEP for Health” intervention (involving individually tailored HIV and PrEP education, motivational interviewing, problem-solving skills and planning, and ongoing navigation support) or an enhanced standard of care (eSOC) control condition involving a brief educational video on the utility of PrEP for HIV prevention. Co-primary outcomes are PrEP uptake (using medical/pharmacy records) and adherence (using tenofovir quantification in hair samples); a secondary outcome is PrEP persistence (using medical/pharmacy records) over 12 months. Major assessments occur at baseline, 1-, 3-, 6-, and 12-month follow-up visits. Planned analyses will examine intervention efficacy, specific hypothesized conceptual mediators of the intervention effect (e.g., self-perceived HIV risk; PrEP knowledge, interest in use, motivation, and behavioral skills) and epidemiologically linked moderators (e.g., age; gender; condomless vaginal or anal sex).

Discussion

Findings from our extensive preliminary research with the study population revealed that a multicomponent, theory-based intervention targeting PrEP knowledge, motivation, self-efficacy, behavioral skills, and structural barriers to PrEP access is urgently needed for PWID who are at risk of HIV acquisition. We also learned that SSPs represent a highly acceptable service setting for delivering such interventions. In this study, we are evaluating the efficacy of the “PrEP for Health” intervention. If efficacious, findings from our implementation evaluation could help guide its dissemination to diverse SSPs and possibly other community-based settings accessed by this population.

Trial registration

ClinicalTrials.gov number NCT04430257, registered June 12, 2020.
Race/ethnicity-specific associations between breastfeeding information source and breastfeeding rates among U.S. women
Authors: Quintero Stephanie M. , Strassle Paula D. , Londoño Tobón Amalia , Ponce Stephanie , Alhomsi Alia , Maldonado Ana I. , Ko Jamie S. , Wilkerson Miciah J. , Nápoles Anna María
Published: March 2023

Background

Despite evidence of the impact of breastfeeding information on breastfeeding rates, it is unknown if information sources and impact vary by race/ethnicity, thus this study assessed race/ethnicity-specific associations between breastfeeding information sources and breastfeeding.

Methods

We used data from the 2016–2019 Pregnancy Risk Assessment Monitoring System. Race/ethnicity-stratified multinomial logistic regression was used to estimate associations between information source (e.g., family/friends) and breastfeeding rates (0 weeks/none, < 10 weeks, or ≥ 10 weeks; < 10 weeks and ≥ 10 weeks = any breastfeeding). All analyses were weighted to be nationally representative.

Results

Among 5,945,018 women (weighted), 88% reported initiating breastfeeding (≥ 10 weeks = 70%). Information from family/friends (< 10 weeks: aORs = 1.58–2.14; ≥ 10 weeks: aORs = 1.63–2.64) and breastfeeding support groups (< 10 weeks: aORs = 1.31–1.76; ≥ 10 weeks: aORs = 1.42–2.77) were consistently associated with breastfeeding and duration across most racial/ethnic groups; effects were consistently smaller among Alaska Native, Black, and Hispanic women (vs White women). Over half of American Indian and one-quarter of Black women reported not breastfeeding/stopping breastfeeding due to return to school/work concerns.

Conclusions

Associations between breastfeeding information source and breastfeeding rates vary across race/ethnicity. Culturally tailored breastfeeding information and support from family/friends and support groups could help reduce breastfeeding disparities. Additional measures are needed to address disparities related to concerns about return to work/school.
Induced leg length inequality affects pelvis orientation during upright standing immediately following a sit-to-stand transfer: a pre-post measurement study
Authors: Vella Simon P. , Swain Michael , Downie Aron , Howarth Samuel J. , Funabashi Martha , Engel Roger M.
Published: March 2023

Background

Leg length inequality (LLI) greater than 20 mm has been associated with low back pain (LBP) and its correction is clinically recommended. Much less is known about the biomechanical effects that LLI below 15 mm has on pelvis orientation.

Methods

Twenty-two adult participants (8 female) aged between 18 and 30 years without LBP were enrolled in the study and completed a series of sit-to-stand trials with no heel-lift (0 mm baseline) and heel-lifts of varying heights (5, 9 and 12 mm) placed in their right shoe. Three-dimensional kinematic data were obtained from the lower extremities, pelvis and thorax. Additional kinematic data were obtained from the left and right sides of the pelvis. The global orientation of the whole pelvis and relative orientation between the left and right sides of the pelvis were obtained in upright standing immediately upon completion of the sit-to-stand movement. Repeated measures ANOVAs were used to detect differences in sample means across the different levels of heel-lift (0, 5, 9, and 12 mm). The tests for within-subject effects determined overall significant differences between the means at the different levels of heel-lift induced LLI. Partial Eta-Squared was used to express the size for the main effect of heel-lift height. For each level of heel-lift, the estimated marginal mean and 95% confidence interval (95%CI) values of pelvis angles were illustrated graphically.

Results

Left frontal plane rotation of the pelvis increased (p = 0.001), that is, the left side of the pelvis was lower than the right side of the pelvis, and anterior tilt of the pelvis decreased (p = 0.020) with a heel-lift height (applied on the right) as low as 5 mm. A significant main effect of heel-lift was only observed for the norm of rotations about all three axes for relative-pelvis orientation (p = 0.034). Post-hoc analyses did not reveal any statistically significant differences between the heel-lifts and the 0 mm baseline (p≥0.072).

Conclusion

These findings suggest that correcting leg length inequality below the recommended threshold of 20 mm may influence pelvic orientation. Future work can investigate the effects of the altered orientations on spine loading and the clinical effects of corrections to minor leg length inequality.
Cost-effectiveness and budget impact of heat-stable carbetocin compared to oxytocin and misoprostol for the prevention of postpartum hemorrhage (PPH) in women giving birth in India
Authors: Cook John R. , Saxena Kunal , Taylor Catharine , Jacobs Jeffrey L.
Published: March 2023

Introduction

Low- and middle-income countries (LMICs) are committed to achieving the Sustainable Development Goal 3.1 to reduce maternal mortality. The Ministry of Health and Family Welfare of India recommends prophylactic uterotonic administration to every woman following delivery to reduce the risk of postpartum hemorrhage (PPH), as PPH is the leading cause of maternal mortality in LMICs, including India. In 2018, the World Health Organization first recognized heat-stable carbetocin for PPH prevention. Governments are now considering its introduction into their public health systems.

Methods

A decision-tree model was developed from the public healthcare system perspective to compare the value of heat-stable carbetocin versus oxytocin and misoprostol among women giving birth in public sector healthcare facilities in India. The model accounted for differences in PPH risk and costs based on mode of delivery and healthcare setting, as well as provider behavior to mitigate quality concerns of oxytocin. Model outcomes for each prophylactic uterotonic included the number of PPH events, DALYs due to PPH, deaths due to PPH, and direct medical care costs. The budget impact was estimated based on projected uterotonic uptake between 2022–2026.

Results

Compared to oxytocin, heat-stable carbetocin avoided 5,468 additional PPH events, 5 deaths, and 244 DALYs per 100,000 births. Projected direct medical costs to the public healthcare system were lowered by US $171,700 (₹12.8 million; exchange rate of ₹74.65 = US$1 from 2 Feb 2022) per 100,000 births. Benefits were even greater when compared to misoprostol (7,032 fewer PPH events, 10 fewer deaths, 470 fewer DALYs, and $230,248 saved per 100,000 births). In the budget impact analysis, India’s public health system is projected to save US$11.4 million (₹849 million) over the next five years if the market share for heat-stable carbetocin grows to 19% of prophylactic uterotonics administered.

Conclusions

Heat-stable carbetocin is expected to reduce the number of PPH events and deaths, avoid more DALYs, and reduce costs to the public healthcare system of India. Greater adoption of heat-stable carbetocin for the prevention of PPH could advance India’s efforts to achieve its maternal health goals and increase efficiency of its public health spending.
Health economic evaluation of preventive digital public health interventions using decision-analytic modelling: a systematized review
Authors: Lange Oliver
Published: March 2023

Background

Digital public health (DiPH) provides novel approaches for prevention, potentially leading to long-term health benefits in resource-limited health systems. However, cost-effectiveness of DiPH interventions is unclear. This systematized review investigates the use of decision-analytic modelling in health economic evaluations of DiPH primary prevention and health promotion interventions, focusing on intervention’s design, methods used, results, and reporting quality.

Methods

PubMed, CINAHL, and Web of Science were searched for studies of decision-analytic economic evaluations of digital interventions in primary prevention or health promotion, published up to June 2022. Intervention characteristics and selected items were extracted based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Incremental cost-effectiveness ratios (ICERs) were then extracted and price-adjusted to compare the economic evaluation results. Finally, the included studies’ reporting quality was assessed by building a score using CHEERS.

Results

The database search (including search update) produced 2,273 hits. After removing duplicates, 1,434 titles and abstracts were screened. Of the 89 studies meeting the full-text search criteria, 14 were ultimately reviewed. The most common targets were physical activity (five studies) and weight loss (four). Digital applications include text messages, web-based inventions, app-based interventions, e-learning devices, and the promotion of smartphone apps. The mean ICER of the 12 studies using quality-adjusted life years (QALYs) is €20,955 per QALY (min. − €3,949; max. €114,211). The mean of reported CHEERS items per study is 81% (min. 59%; max. 91%).

Conclusions

This review only includes primary prevention and health promotion, and thus excludes other DiPH fields (e.g. secondary prevention). It also focuses on decision-analytic models, excluding study-based economic evaluations. Standard methods of economic evaluation could be adapted more to the specifics of DiPH by measuring the effectiveness of more current technologies through alternative methods, incorporating a societal perspective, and more clearly defining comparators. Nevertheless, the review demonstrates using common thresholds that the new field of DiPH shows potential for cost-effective preventive interventions.
Systematic evaluation of membrane-camouflaged nanoparticles in neutralizing Clostridium perfringens ε-toxin
Authors: Xu Jinglin , Li Dongxue , Kang Lin , Liu Tingting , Huang Jing , Li Jiaxin , Lv Jing , Wang Jing , Gao Shan , Li Yanwei , Yuan Bing , Zhao Baohua , Wang Jinglin , Xin Wenwen
Published: March 2023

Clostridium perfringens ε-toxin (ETX) is the main toxin leading to enterotoxemia of sheep and goats and is classified as a potential biological weapon. In addition, no effective treatment drug is currently available in clinical practice for this toxin. We developed membrane-camouflaged nanoparticles (MNPs) with different membrane origins to neutralize ETX and protect the host from fatal ETX intoxication. We evaluated the safety and therapeutic efficacy of these MNPs in vitro and in vivo. Compared with membranes from karyocytes, such as Madin-Darby canine kidney (MDCK) cells and mouse neuroblastoma N2a cells (N2a cells), membrane from erythrocytes, which do not induce any immune response, are superior in safety. The protective ability of MNPs was evaluated by intravenous injection and lung delivery. We demonstrate that nebulized inhalation is as safe as intravenous injection and that both modalities can effectively protect mice against ETX. In particular, pulmonary delivery of nanoparticles more effectively treated the challenge of inhaled toxins than intravenously injected nanoparticles. Moreover, MNPs can alter the biological distribution of ETX among different organs in the body, and ETX was captured, neutralized and slowly delivered to the liver and spleen, where nanoparticles with ETX could be phagocytized and metabolized. This demonstrates how MNPs treat toxin infections in vivo. Finally, we injected the MNPs into mice in advance to find out whether MNPs can provide preventive protection, and the results showed that the long-cycle MNPs could provide at least a 3-day protection in mice. These findings demonstrate that MNPs provide safe and effective protection against ETX intoxication, provide new insights into membrane choices and delivery routes of nanoparticles, and new evidence of the ability of nanoparticles to provide preventive protection against infections.

Graphical Abstract
An integrated approach of network pharmacology, molecular docking, and experimental verification uncovers kaempferol as the effective modulator of HSD17B1 for treatment of endometrial cancer
Authors: Ruan Guan-Yu , Ye Li-Xiang , Lin Jian-Song , Lin Hong-Yu , Yu Li-Rui , Wang Cheng-Yan , Mao Xiao-Dan , Zhang Shui-Hua , Sun Peng-Ming
Published: March 2023

Background

Endometrial cancer (EC) is one of the most common gynecological malignancies globally, and the development of innovative, effective drugs against EC remains a key issue. Phytoestrogen kaempferol exhibits anti-cancer effects, but the action mechanisms are still unclear.

Method

MTT assays, colony-forming assays, flow cytometry, scratch healing, and transwell assays were used to evaluate the proliferation, apoptosis, cell cycle, migration, and invasion of both ER-subtype EC cells. Xenograft experiments were used to assess the effects of kaempferol inhibition on tumor growth. Next-generation RNA sequencing was used to compare the gene expression levels in vehicle-treated versus kaempferol-treated Ishikawa and HEC-1-A cells. A network pharmacology and molecular docking technique were applied to identify the anti-cancer mechanism of kaempferol, including the building of target-pathway network. GO analysis and KEGG pathway enrichment analysis were used to identify cancer-related targets. Finally, the study validated the mRNA and protein expression using real-time quantitative PCR, western blotting, and immunohistochemical analysis.

Results

Kaempferol was found to suppress the proliferation, promote apoptosis, and limit the tumor-forming, scratch healing, invasion, and migration capacities of EC cells. Kaempferol inhibited tumor growth and promotes apoptosis in a human endometrial cancer xenograft mouse model. No significant toxicity of kaempferol was found in human monocytes and normal cell lines at non-cytotoxic concentrations. No adverse effects or significant changes in body weight or organ coefficients were observed in 3–7 weeks’ kaempferol-treated animals. The RNA sequencing, network pharmacology, and molecular docking approaches identified the overall survival-related differentially expressed gene HSD17B1. Interestingly, kaempferol upregulated HSD17B1 expression and sensitivity in ER-negative EC cells. Kaempferol differentially regulated PPARG expression in EC cells of different ER subtypes, independent of its effect on ESR1. HSD17B1 and HSD17B1-associated genes, such as ESR1, ESRRA, PPARG, AKT1, and AKR1C1\2\3, were involved in several estrogen metabolism pathways, such as steroid binding, 17-beta-hydroxysteroid dehydrogenase (NADP+) activity, steroid hormone biosynthesis, and regulation of hormone levels. The molecular basis of the effects of kaempferol treatment was evaluated.

Conclusions

Kaempferol is a novel therapeutic candidate for EC via HSD17B1-related estrogen metabolism pathways. These results provide new insights into the efficiency of the medical translation of phytoestrogens.
Endocannabinergic modulation of central serotonergic activity in healthy human volunteers
Authors: Emons Barbara , Arning Larissa , Makulla Vera-Estelle , Suchy Maria-Theresia , Tsikas Dimitrios , Lücke Thomas , Epplen Jörg T. , Juckel Georg , Roser Patrik
Published: March 2023

Background

The serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers.

Methods

Serotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method.

Results

Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed.

Conclusions

Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.
Effects of repetitive functional magnetic stimulation in the sacral nerve in patients with neurogenic detrusor overactivity after suprasacral spinal cord injury: a study protocol for a randomized controlled trial
Authors: Li Jiyang , Wang Jianxiong , Hu Yue , Jian Rui , Zhao Yulu , Li Dan , Wan Tenggang , Jike Wuga , Xu Fangyuan , Huang Maomao
Published: March 2023

Background

Neurogenic detrusor overactivity (NDO) is a serious and common complication after spinal cord injury, affecting patients’ quality of life seriously. Therefore, we developed this research protocol to evaluate the efficacy of repetitive functional magnetic stimulation (rFMS) in the sacral nerve in patients with neurogenic detrusor overactivity (NDO) after suprasacral spinal cord injury (SCI) and provide more options for rFMS in treating NDO after suprasacral SCI.

Methods

This study is a single-center, randomized, parallel-group clinical trial. We will recruit the patients with NDO after suprasacral SCI in the Rehabilitation Department of the Affiliated Hospital of Southwest Medical University from September 2022 to August 2023. They will be assigned to the rFMS group and the sham stimulation group randomly. The sample size is 66, with 33 patients in each group. The rFMS group will receive real rFMS treatment of the sacral nerve (100% stimulation intensity, 5 Hz, 20 min each time, five times a week), and the sham group will receive sham stimulation. Both groups will receive similar treatment strategies, including medication, standard urine management, acupuncture treatment, and health education. The bladder compliance (bladder capacity/detrusor pressure) and pudendal nerve electromyography will be evaluated at baseline, 8th week of treatment. The residual volume of the bladder and bladder diary will be recorded once a week during 8 weeks of treatments. SCI-QOL and NBSS will be evaluated at baseline, the 4th and 8th week of treatment. In addition, the above assessments will be followed up at 8 weeks after the end of treatment.

Discussion

It is expected that the bladder function, symptoms, and quality of life might be significantly improved after rFMS of the sacral nerve.

Trial registration

The China Clinical Trials Registry has approved this study, registration number: ChiCTR2100045148. Registered on April 7, 2021.
Extensive prevalence and significant genetic differentiation of Blastocystis in high- and low-altitude populations of wild rhesus macaques in China
Authors: Yu Mengshi , Yao Yongfang , Xiao Hongtao , Xie Meng , Xiong Ying , Yang Shengzhi , Ni Qingyong , Zhang Mingwang , Xu Huailiang
Published: March 2023

Background

Blastocystis is a common intestinal protist with a wide range of hosts. Thus far, 38 subtypes have been identified. In recent years, wild animals have been confronted with habitat fragmentation as well as an increasing risk of zoonotic disease transmission due to human disturbance. Only limited data are available on Blastocystis infection and subtype distribution in wild rhesus macaques in China. The aim of the present study was to investigate the prevalence and genetic diversity of Blastocystis in nine wild rhesus macaque populations in China.

Methods

A total of 276 faecal samples were collected from five high-altitude populations (high-altitude group [HAG]; 2800–4100 m a.s.l.) and four low-altitude populations (low-altitude group [LAG]; 5–1000 m a.s.l) of rhesus macaques. PCR-based analysis, using a new primer pair for the amplification of a 1690-bp sequence of the small subunit ribosomal RNA (SSU rRNA) gene, was used for prevalence and genetic diversity analysis.

Result

Analysis of faecal samples revealed that Blastocystis infection was common in rhesus macaques, with an infection positivity rate of 80.1% (n = 221/276 samples). There was no significant difference (P = 0.121) in positivity rate between the LAG (84.3%) and HAG (76.8%). Overall, 33 haplotypes were obtained and classified into four subtypes (STs), of which three were potentially zoonotic subtypes (ST1, 29.7%; ST2, 16.7%; ST3, 31.9%) and one that was first identified in this study and named ST39 (12.0%). The STs were distributed differently among the rhesus macaque populations, except for ST3, which was found in all populations. Phylogenetic analyses revealed two major divergent clades of ST3 for the HAG and LAG. Genetic diversity analysis showed a high genetic diversity of ST3 (haplotype diversity: 0.846; nucleotide diversity: 0.014) in the rhesus macaques, but a high genetic differentiation (FST > 0.25) and a low gene flow (Nm = 0.09) between the HAG and LAG.

Conclusion

Our study, which is the first investigation on Blastocystis infection in multiple wild rhesus macaque populations in China, indicates a potential risk of zoonotic transmission of Blastocystis in the study areas. Blastocystis ST3 showed high genetic diversity in wild rhesus macaques and significant genetic differentiation between the HAG and LAG. Our results provide fundamental information on the genetic diversity and prevalence of Blastocystis in wild rhesus macaque populations.

Graphical Abstract
Cryptococcus neoformans, a global threat to human health
Authors: Zhao Youbao , Ye Leixin , Zhao Fujie , Zhang Lanyue , Lu Zhenguo , Chu Tianxin , Wang Siyu , Liu Zhanxiang , Sun Yukai , Chen Min , Liao Guojian , Ding Chen , Xu Yingchun , Liao Wanqing , Wang Linqi
Published: March 2023

Background

Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL,Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.

Methods

We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keywordCryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance ofC. neoformansto approved antifungal drugs.

Results

There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden.

Conclusion

The rising threat ofC. neoformansis compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.
Natural world heritage conservation and tourism: a review
Authors: Zhang Zhenzhen , Xiong Kangning , Huang Denghong
Published: March 2023

The trade-off and synergy between heritage conservation and tourism has become the focus of natural world heritage research. To gain a better understanding of the global researches on natural World Heritage conservation and tourism, we comprehensively reviewed relevant peer-reviewed research literature based on Web of Science (WOS) and China National Knowledge Infrastructure (CNKI). We find that (1) the theoretical research of natural heritage conservation and tourism has gone through a process from emphasizing the protection of heritage value to pursuing the synergy of heritage protection and tourism development; (2) the main research methods include investigation research methods, indirect research methods and experimental research methods; (3) "3S" technology (remote sensing, geographic information system, global positioning system), three-dimensional laser scanning technology, virtual reality (VR) technology, augmented reality (AR) technology, holographic projection technology and other modern technological means are applied to the protection and tourism development of natural properties; (4) the common coordinated development models include ecological science tourism, community participation in tourism, ecological compensation model, world heritage—buffer zone—surrounding areas coordinated protection model and so on. We analyzed the research progresses through (1) the theories proposed in the literature, (2) the main methods applied to address the issues on natural heritage conservation and tourism, (3) the technologies applied in the researches and (4) the coordinated models of heritage conservation and tourism. Furthermore, we put forward the following research prospects: (1) systematically explore the conservation methods and theories based on world heritage criteria; (2) formulate corresponding conservation systems and ecological restoration standards for different types of world heritage; (3) give full play to the complementary advantages of various research methods and reveal the mutual feedback mechanism between tourism and heritage conservation; (4) develop ecological restoration technology based on biodiversity restoration, establish radial ecological corridor, and expand the benign ecological environment of the properties to wider periphery; (5) build ecological compensation development models based on the perspective of heritage tourism and value realization of world heritage.
Anisotropy of impact ionization in WSe2 field effect transistors
Authors: Kang Taeho , Choi Haeju , Li Jinshu , Kang Chanwoo , Hwang Euyheon , Lee Sungjoo
Published: March 2023

Carrier multiplication via impact ionization in two-dimensional (2D) layered materials is a very promising process for manufacturing high-performance devices because the multiplication has been reported to overcome thermodynamic conversion limits. Given that 2D layered materials exhibit highly anisotropic transport properties, understanding the directionally-dependent multiplication process is necessary for device applications. In this study, the anisotropy of carrier multiplication in the 2D layered material, WSe2, is investigated. To study the multiplication anisotropy of WSe2, both lateral and vertical WSe2 field effect transistors (FETs) are fabricated and their electrical and transport properties are investigated. We find that the multiplication anisotropy is much bigger than the transport anisotropy, i.e., the critical electric field (ECR) for impact ionization of vertical WSe2 FETs is approximately ten times higher than that of lateral FETs. To understand the experimental results we calculate the average energy of the carriers in the proposed devices under strong electric fields by using the Monte Carlo simulation method. The calculated average energy is strongly dependent on the transport directions and we find that the critical electric field for impact ionization in vertical devices is approximately one order of magnitude larger than that of the lateral devices, consistent with experimental results. Our findings provide new strategies for the future development of low-power electric and photoelectric devices.

Graphical Abstract
Evaluation of a real-time mobile PCR device (PCR 1100) for the detection of the rabies gene in field samples
Authors: Demetria Catalino , Kimitsuki Kazunori , Yahiro Takaaki , Saito Nobuo , Hashimoto Takehiro , Khan Sakirul , Chu Maria Yna Joyce , Manalo Daria , Mananggit Milagros , Quiambao Beatriz , Nishizono Akira
Published: March 2023

Background

The Philippines is ranked among the top countries with 200–300 annual deaths due to rabies. Most human rabies cases have been reported in remote areas, where dog surveillance is inadequate. Therefore, a strategy to effectively improve surveillance in remote areas will increase the number of detections. Detecting pathogens using portable real-time reverse transcription-polymerase chain reaction (RT-PCR) has the potential to be accepted in these areas. Thus, we aimed to develop an assay to detect the rabies virus (RABV) genome by combining the robust primer system LN34 with the PicoGene PCR1100 portable rapid instrument targeting RABV RNA (PCR1100 assay).

Methods

Procedures were optimised using an LN34 primer/probe set, KAPA3G Plant PCR Kit (KAPA Biosystems), FastGene Scriptase II (NIPPON Genetics), and an artificial positive control RNA.

Results

Positive control RNA showed an analytical limit of detection of 10 copies/µL without false positivity, generating results in approximately 32 min. Compared to dFAT or RT-qPCR using field samples, the sensitivity and specificity of the PCR1100 assay were 100%, and even lower copy numbers (approximately 10 copies/µL) were detected.

Conclusions

This study demonstrated that the developed assay can detect rabies RNA in field samples. Because dog-mediated rabies is endemic in remote areas, the rapidity, mobility, and practicality of the PCR1100 assay as well as the high sensitivity of the LN34 system make it an ideal tool for the confirmation of rabies in these areas.
Wild mushroom consumption in the P’urhépecha Plateau at Michoacán, México: social, ethnomycological and nutritional issues
Authors: Torres-Gómez Mariano , Gómez-Peralta Marlene , Vázquez-Marrufo Gerardo
Published: March 2023

Among Mesoamerican cultures, P’urhépecha settlers inhabiting Michoacán State in Central Mexico preserve ancestral tradition on mushrooms eating. Most mycological knowledge available for this ethnical group has been addressed in the Pátzcuaro’s Lake zone, whereas P’urhépecha communities in other cultural and ecological relevant geographic areas remain unstudied. Thus, this work describes the ethnomycological knowledge of a scarcely analyzed Arantepacua P’urhépecha community at Michoacán Plateau region. Through structured interviews and field collections, data on the use, knowledge, biomass extraction and nomenclature of wild mushrooms were obtained. A list of P’urhépecha names to design 16 wild mushrooms species and 11 fruitbody components is documented and studied community used Spanish popular names to describe 21 wild mushrooms species and 11 fruitbody structures. Most valuable consumed mushroom species for Arantepacua settlers belong to the Amanita, Boletus, Hypomyces and Ramaria genera. Gender roles on mushrooms collect and cooking, new terms in P’urhépecha dialect to refer the parts of a fruitbody and vegetative mycelium, as well as local recipes and nutritional relevance of the mushroom species consumed by studied community are addressed and discussed. The ethnomycological knowledge documented contributes new terms in P’urhépecha to name the parts of an agarical fruitbody, the mycelium and empirical knowledge about mycorrhizal associations. This was the first P’urhépecha ethnomycological study made outside the Lake Pátzcuaro basin.
The diagnostic accuracy of an inclusive three-window ultrasonography assessment for the rapid authentication of endotracheal tube position in RICU
Authors: Sayed Islam G. , Salama Suzan , Abdallah Marwa
Published: March 2023

Background

Assurance of proper endotracheal tube (ETT) location is crucial immediately after intubation as undiagnosed esophageal intubation can be catastrophic. The primary purpose for this study is to determine the diagnostic accuracy of to evaluate the accuracy of an inclusive three-window ultrasonography assessment for the rapid authentication of endotracheal tube position in the intensive care unit (RICU) with reference to Co2monitors (capnography) (the gold standard technique), The study included 100 patients who needed emergency intubation in the ICU of Aswan university hospital. Upon entrance to ICU, intubations was done by the residents and collective bedside three-windows ultra-sonography (tracheal, lung, diaphragmatic ultra-sonography) was carried out instantly after intubation Subsequently, the correct position of the endotracheal tube was established by the resident investigator via the use a capnometer.

Results

Waveform capnography revealed endotracheal intubation in 80 cases (80%) and esophageal intubation in 20 cases (20%). However, trans-tracheal ultra-sonography (TUS) was able to detect endotracheal intubation in 78 cases (78%) and esophageal intubation in 22 cases (22%) patients. SLS detected only 17 esophageal intubations from 20 cases detected by CO2 detectors. DUS was able to detect proper endotracheal intubation in 77 cases (77%) and esophageal intubation in 23 cases (23%). However, it detected only 17 esophageal intubations from 20 cases detected by Co2detectors.

Conclusions

Ultra-sonography, as recently introduced practice for validation of correct endotracheal tube location has both high accuracy and safety profile and can be used as a primary authentication technique.

Trial registration

NCT05747248
Long-Term Performance of an Image-Based Short-Term Risk Model for Breast Cancer
Authors: Eriksson Mikael , Czene Kamila , Vachon Celine , Conant Emily F. , Hall Per
Published: March 2023

PURPOSE

Image-derived artificial intelligence–based short-term risk models for breast cancer have shown high discriminatory performance compared with traditional lifestyle/familial-based risk models. The long-term performance of image-derived risk models has not been investigated.

METHODS

We performed a case-cohort study of 8,604 randomly selected women within a mammography screening cohort initiated in 2010 in Sweden for women age 40-74 years. Mammograms, age, lifestyle, and familial risk factors were collected at study entry. In all, 2,028 incident breast cancers were identified through register matching in May 2022 (206 incident breast cancers were found in the subcohort). The image-based model extracted mammographic features (density, microcalcifications, masses, and left-right breast asymmetries of these features) and age from study entry mammograms. The Tyrer-Cuzick v8 risk model incorporates self-reported lifestyle and familial risk factors and mammographic density to estimate risk. Absolute risks were estimated, and age-adjusted AUC model performances (aAUCs) were compared across the 10-year period.

RESULTS

The aAUCs of the image-based risk model ranged from 0.74 (95% CI, 0.70 to 0.78) to 0.65 (95% CI, 0.63 to 0.66) for breast cancers developed 1-10 years after study entry; the corresponding Tyrer-Cuzick aAUCs were 0.62 (95% CI, 0.56 to 0.67) to 0.60 (95% CI, 0.58 to 0.61). For symptomatic cancers, the aAUCs for the image-based model were ≥0.75 during the first 3 years. Women with high and low mammographic density showed similar aAUCs. Throughout the 10-year follow-up, 20% of all women with breast cancers were deemed high-risk at study entry by the image-based risk model compared with 7.1% using the lifestyle familial-based model ( P < .01).

CONCLUSION

The image-based risk model outperformed the Tyrer-Cuzick v8 model for both short-term and long-term risk assessment and could be used to identify women who may benefit from supplemental screening and risk reduction strategies.
Approach to the Patient With a Suboptimal Statin Response: Causes and Algorithm for Clinical Management
Authors: Sun Lufan , Wolska Anna , Amar Marcelo , Zubirán Rafael , Remaley Alan T
Published: March 2023

Context

Statins are the lipid-lowering therapy of choice for the prevention of atherosclerotic cardiovascular disease (ASCVD) but their effectiveness in lowering low-density lipoprotein cholesterol (LDL-C) can substantially differ between individuals. In this mini-review, we describe the different causes for a suboptimal statin response and an algorithm for the diagnosis and clinical management of these patients.

Evidence Acquisition

A PubMed search using the terms “statin resistance,” “statin sensitivity,” “statin pharmacokinetics,” “cardiovascular disease,” and “lipid-lowering therapies” was performed. Published papers in the past 10 years that were relevant to the topic were examined to provide content for this mini-review.

Evidence Synthesis

Suboptimal lowering of LDL-C by statins is a major problem in the clinical management of patients and limits the value of this therapeutic approach. There are multiple causes of statin hyporesponsiveness with compliance being the most common explanation. Other causes, such as analytical issues with LDL-C measurement and the presence of common lipid disorders (familial hypercholesterolemia, elevated lipoprotein[a] and secondary dyslipidemias) should be excluded before considering primary statin resistance from rare genetic variants in lipoprotein-related or drug-metabolism genes. A wide variety of nonstatin lipid-lowering drugs are now available and can be added to statins to achieve more effective LDL-C lowering.

Conclusions

The evaluation of statin hyporesponsiveness is a multistep process that can lead to the optimization of lipid-lowering therapy for the prevention of ASCVD. It may also lead to the identification of distinct types of dyslipidemias that require specific therapies and/or the genetic screening of family members.
The Changing Face of Multiple Endocrine Neoplasia 2A: From Symptom-Based to Preventative Medicine
Authors: Machens Andreas , Lorenz Kerstin , Brandenburg Tim , Führer-Sakel Dagmar , Weber Frank , Dralle Henning
Published: March 2023

Context

Early genetic association studies yielded too high risk estimates for multiple endocrine neoplasia (MEN2A), suggesting a need for extended surgery.

Objective

The objective was to delineate temporal changes in MEN2A presentation by birth cohort analyses.

Methods

Birth cohort analyses (10-year increments; ≤1950 to 2011-2020) of carriers of rearranged during transfection (RET) mutations who underwent surgery for MEN2A.

Results

Included in this study were 604 carriers (155 index, 445 nonindex, 4 additional patients), with 237 carriers harboring high-risk mutations, 165 carriers moderate–high risk mutations, and 202 carriers low–moderate risk mutations. With increasing recency of birth cohorts, there was a continual decline in index patients from 41-74% to 0% (P < .001) and of medullary thyroid cancer (MTC) from 96-100% to 0-33% (P < .001). Node metastases diminished from 62-70% to 0% (P ≤ .001; high and low–moderate risk mutations), whereas biochemical cure after thyroidectomy surged from 17-33% to 100% (P ≤ .019; high and low–moderate mutations). Surgical interventions for MEN2A-related tumors were performed increasingly earlier, causing median carrier age to fall: from 51-63 to 3-5 years at thyroidectomy (P < .001); from 46-51 to 24-25 years at first adrenalectomy (P ≤ .013; high and moderate–high risk mutations); and from 43.5-66 to 16.5-32 years at parathyroidectomy. MTC diameters were more effectively decreased from 14-32 to 1-4 mm (P ≤ 002) than pheochromocytoma diameters (nonsignificant).

Conclusion

These insights into MEN2A presentation, adjusted by birth year, illustrate the shift from reactive to preventative medicine, enabling less extensive risk-reducing surgery.
Altered Emotion Perception Linked to Structural Brain Differences in Youth With Congenital Adrenal Hyperplasia
Authors: Omary Adam , Khalifeh Noor , Cotter Devyn L , Kim Mimi S , Choudhury Farzana , Ahmadi Hedyeh , Geffner Mitchell E , Herting Megan M
Published: March 2023

Context

Congenital adrenal hyperplasia (CAH) is a genetic disorder that results in hormonal imbalances and decreased brain volumes in regions important for emotional processing.

Objective

To examine whether emotion perception differs between youth with CAH and control youth, and if these differences relate to brain volumes.

Methods

In this cross-sectional study of 27 youths with CAH (mean age = 12.63 years, 16 female) and 35 age- and sex-matched controls (mean age = 13.03 years, 20 female), each participant rated picture stimuli and completed a 3T structural brain scan. Valence and arousal ratings and reaction times of 61 affective images were assessed. Gray matter volumes were measured by MRI.

Results

Youth with CAH had lower valence ratings for negative (P = .007) and neutral (P = .019) images. Controls showed differences in reaction times and arousal ratings across stimuli conditions, but youth with CAH did not. Brain volumes of the right amygdala (P = .025) and left hippocampus (P = .002) were associated with valence ratings. Left rostral middle frontal (P < .001) and right medial orbitofrontal cortex (P = .002) volumes were negatively related to valence scores only in youth with CAH, whereas left medial orbitofrontal cortex (P < .001) volumes were associated with valence scores positively in youth with CAH and negatively in controls.

Conclusion

Findings suggest that youth with CAH perceive emotive stimuli as more unpleasant. Decreased brain volumes in the amygdala, hippocampus, and prefrontal cortex are associated with these measures of altered emotion perception in youth with CAH.
Casein Kinase 1α Regulates Testosterone Synthesis and Testis Development in Adult Mice
Authors: Guo Hongzhou , Zhang Di , Zhou Yewen , Sun Longjie , Li Changping , Luo Xuan , Liu Jiali , Cui Sheng
Published: March 2023

Casein kinase 1α (CK1α) is a main component of the Wnt/β-catenin signaling pathway, which participates in multiple biological processes. Our recent study demonstrated that CK1α is expressed in both germ cells and somatic cells of mouse testes and regulates spermatogenesis. However, little information is known about the role of CK1α in regulating the development of somatic cells in mouse testes. Our results demonstrated that conditional disruption of CK1α in murine Leydig cells sharply decreased testosterone levels; markedly affected testis development, sperm motility, and sperm morphology; and caused subfertility. The germ cell population was partially decreased in CK1α conditional knockout (cKO) mice, while the proliferation of Leydig cells and Sertoli cells was not affected. Furthermore, in vitro results verified that luteinizing hormone upregulates CK1α through the luteinizing hormone/protein kinase/Epidermal Growth Factor Receptor/extracellular regulated protein kinases/2 signaling pathway and that CK1α interacts with and phosphorylates EGFR, which subsequently activates the phosphorylation of ERK1/2, thereby promoting testosterone synthesis. In addition, high-dose testosterone propionate partially rescued the phenotype observed in cKO mice. This study provides new insights into the role of CK1α in steroidogenesis and male reproduction.