bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of virtual reality-based cue exposure therapy on craving and physiological responses in alcohol-dependent patients-a randomised controlled trial
Authors: Zhang Junjun , Chen Ming , Yan Junli , Wang Chaojun , Deng Hongdu , Wang Jiali , Gu Jiapeng , Wang Dan , Li Wenhui , Wang Chuansheng
Published: December 2023

Background

Cue exposure therapy is used to treat alcohol dependence. However, its effectiveness is controversial due to the limitations of the clinical treatment setting. Virtual reality technology may improve the therapeutic effect. The aim of this study is to explore whether virtual reality-based cue exposure therapy can reduce the psychological craving and physiological responses of patients with alcohol dependence.

Methods

Forty-four male alcohol-dependent patients were recruited and divided into the study group (n = 23) and the control group (n = 21) according to a random number table. The control group received only conventional clinical treatment for alcohol dependence. The study group received conventional clinical treatment with the addition of VR cue exposure (treatment). The primary outcome was to assess psychological craving and physiological responses to cues of patients before and after treatment.

Results

After virtual reality-based cue exposure therapy, the changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those in the control group (P < 0.05), while the changes in skin conductance and respiration between the study group and the control group were not significantly different (P > 0.05). The changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those before treatment (P < 0.05), while the changes in skin conductance and respiration were not significantly different from those before treatment (P > 0.05). The changes in VAS, heart rate, skin conductance and respiration before and after cue exposure in the control group were not significantly different from those before treatment (P > 0.05).

Conclusion

Virtual reality-based cue exposure therapy can reduce the psychological craving and part of the physiological responses of alcohol-dependent patients during cue exposure in the short term and may be helpful in the treatment of alcohol dependence.

Trial registration

The study protocol was registered at the China Clinical Trial Registry on 26/02/2021 (www.chictr.org.cn; ChiCTR ID: ChiCTR2100043680).
Parents’ hope in perinatal and neonatal palliative care: a scoping review
Authors: Silveira Aline Oliveira , Wernet Monika , Franco Larissa Fernandes , Dias Patrícia Luciana Moreira , Charepe Zaida
Published: December 2023

Background

The diagnosis of a life-limiting condition of a child in the perinatal or neonatal period is a threat to parental hopes. Hope is an interactional and multidimensional construct, and in palliative care, it is a determinant of quality of life, survival, acceptance and peaceful death.

Objective

To map scientific evidence on parents’ hope in perinatal and neonatal palliative care contexts.

Method

a scoping review theoretically grounded on Dufault and Martocchio’s Framework, following the Joanna Briggs Institute methodological recommendations. Searches were performed until May 2023 in the MEDLINE, CINAHL and PsycINFO databases. The searches returned 1341 studies.

Results

Eligible papers included 27 studies, most of which were carried out in the United States under a phenomenological or literature review approach. The centrality of women’s perspectives in the context of pregnancy and perinatal palliative care was identified. The parental hope experience is articulated in dealing with the uncertainty of information and diagnosis, an approach to which interaction with health professionals is a determinant and potentially distressful element. Hope was identified as one of the determinants of coping and, consequently, linked to autonomy and parenthood. Cognitive and affiliative dimensions were the hope dimensions that predominated in the results, which corresponded to the parents’ ability to formulate realistic goals and meaningful interpersonal relationships, respectively.

Conclusion

Hope is a force capable of guiding parents along the path of uncertainties experienced through the diagnosis of a condition that compromises their child’s life. Health professionals can manage the family’s hope by establishing sensitive therapeutic relationships that focus on the dimension of hope. The need for advanced research and intervention in parental and family hope are some of the points made in this study.

Protocol registration

https://osf.io/u9xr5/.
Assessment of knowledge and practices of exclusive breastfeeding among rural women during the COVID-19 pandemic in Egypt: a cross sectional study
Authors: El-Gamel Noura , El-Nemer Amina
Published: December 2023

Background

Worldwide exclusive breastfeeding is still recommended as a successful strategy even during the COVID -19 pandemic to lower infant morbidity and mortality. This study aimed to assess the knowledge and practices of exclusive breastfeeding among rural women during the COVID-19 pandemic.

Methods

A descriptive cross-sectional study was conducted at EL-Morabeen Family Medicine Center in rural Damietta, Egypt among 178 lactating women who were chosen by using the purposive sampling technique. A developed structured questionnaire consisting of four parts was used to gather data from March to May 2022. Univariate analysis for descriptive data and bivariate analysis through the chi-square test were performed.

Results

The current study revealed that 73% of the studied rural women did not receive any breastfeeding counseling during antenatal visits and 61.2% of them believed that coronavirus was transmitted through breastmilk. Only 15.2% of them breastfed their infant exclusively for 6 months, 88.2% of mothers delayed breastfeeding initiation after delivery and 48.3% administered the prelacteal feeds. A total of 98.3% of rural women had never made skin-to-skin contact, and 79.2% of them had not been vaccinated against COVID-19. Additionally, a statistically significant association between good knowledge and practice with highly educated women aged 26–30 years, with a monthly income of 4000–6000 L.E was found. Furthermore, only 26.4% and 26.1% of rural women had good knowledge and practice scores respectively.

Conclusion

Suboptimal breastfeeding practices, such as delayed onset of breastfeeding, low percentages of exclusivity, early weaning, prelacteal feeding administration, and lack of skin-to-skin contact during the COVID -19 pandemic were prevalent among the studied rural mothers. Breastfeeding counseling for all pregnant women and implementation of evidence-based practices in the health care system, such as the early initiation of breastfeeding and skin-to-skin contact, are recommended.
BodyThink program-based body image education improves Korean adolescents’ attitudes toward cosmetic surgery: randomized controlled trial
Authors: Sung Hyeonhwa , Han A Young , Seol Geun Hee
Published: December 2023

Background

The aims of this study were to modify the widely used BodyThink program to suit the circumstances of Korean schools and determine its effects on body esteem, body image, appearance stress, depression, and attitudes toward cosmetic surgery.

Methods

Participants were 184 third-grade students from two middle schools in Korea, who were randomly assigned to a control or intervention group. Two of the participants dropped out; hence, data from 182 students were analyzed. The control group received the existing curriculum for 4 sessions, and the experimental group was provided with 4 sessions of the revised BodyThink program. Before and after the intervention, all participants completed questionnaires.

Results

In the BodyThink group, improved body image, decreased depression, and positive improvements in attitudes toward cosmetic plastic surgery were observed after the intervention.

Discussion

These results suggest that school health nurses can utilize interventions based on BodyThink program in their curricula to improve the physical and emotional health of adolescents.

Trial registration

This study has been retrospectively registered with the Clinical Research information Service (CRIS) in Korea on October 5, 2023 (KCT0008839).
Community perceptions of a biopsychosocial model of integrated care in the health center: the case of 4 health districts in South Kivu, Democratic Republic of Congo
Authors: Kasongo Bertin , Mukalay Abdon , Molima Christian , Makali Samuel Lwamushi , Chiribagula Christian , Mparanyi Gérard , Karemere Hermès , Bisimwa Ghislain , Macq Jean
Published: December 2023

Background

Biopsychosocial care is one of the approaches recommended in the health system by the WHO. Although efforts are being made on the provider side to implement it and integrate it into the health system, the community dynamic also remains to be taken into account for its support. The objective of this study is to understand the community's perceptions of the concept of integrated health care management according to the biopsychosocial approach (BPS) at the Health Center of a Health District and its evaluation in its implementation.

Methods

This cross-sectional study was done in six Health Areas belonging to four Health Districts in South Kivu, DRC. We conducted 15 semi-directive individual interviews with 9 respondents selected by convenience, including 6 members of the Development Committees of the Health Areas, with whom we conducted 12 interviews and 3 patients met in the health centers. The adapted Normalization MeAsure Development (NoMAD) tool, derived from the Theory of the Normalization Process of Complex Interventions, allowed us to collect data from November 2017 to February 2018, and then from November 2018 to February 2019. After data extraction and synthesis, we conducted a thematic analysis using the NoMAD tool to build a thematic framework. Six themes were grouped into three categories.

Results

Initially, community reports that the BPS approach of integrated care in the Health Centre is understood differently by providers; but then, through collective coordination and integrated leadership within the health care team, the approach becomes clearer. The community encouraged some practices identified as catalysts to help the approach, notably the development of financial autonomy and mutual support, to the detriment of those identified as barriers. According to the community, the BPS model has further strengthened the performance of health workers and should be expanded and sustained.

Conclusions

The results of our study show the importance of community dynamics in the care of biopsychosocial situations by providers. The barriers and catalysts to the mechanism, both community-based and professional, identified in our study should be considered in the process of integrating the biopsychosocial model of person-centered health care.
Prevalence and first molecular identification of Sarcocystis species in feces of domestic dogs (Canis familiaris) in Egypt
Authors: Elshahawy Ismail S. , Fawaz Marwa , Gomaa Aya , Mohammed Eman
Published: December 2023

Background

Sarcocystis species are obligatorily heteroxenous protozoan parasites with predator–prey life cycles. Global Knowledge about the epidemiology and the distribution pattern of different Sarcocystis species in dog feces are very scarce. Therefore, the current investigation was conducted to declare the occurrence of Sarcocystis in the fecal specimens of the most common canids in Egypt, the domestic dogs, and to identify the species present using various parasitological and molecular approaches.

Methods

A total of 100 dog fecal samples were collected and screened using fecal sugar flotation test for the presence of Sarcocystis oocysts/sporocysts. Additionally, thirty samples were used for genomic DNA extraction. The 18S rRNA gene fragment was the target of primers for a PCR, followed by purification and sequencing of the amplicons.

Results

Currently, the results obtained reviewed that 4% of fecal samples were positive for Sarcocystis spp. using LM. Additionally, Sarcocystis spp. were verified in sixteen dogs (53.3%, 16/30) using PCR and subsequent sequencing protocols. Statistically, insignificant difference in prevalence of sarcocystosis relative to age and gender was noticed. Morphologically, the detected sporocysts measured 13.2–16.0 × 9.4–11 μm. Based on the 18S rRNA gene, sequencing analysis of amplicons from sporocysts DNA revealed 99.82% nucleotide homology with published S. tenella partial nucleotide sequences from sheep in Iraq and Iran.

Conclusions

This is the first molecular evidence in support of the final host role of domestic dogs in the life cycle of S. tenella in Egypt, which provides a precious diagnostic tool for further epidemiological studies and for the assessment of the effectiveness of control measures for this disease.
Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models
Authors: He Yan , Li Ruohan , She Wenting , Ai Yilong , Li Kesheng , Kumeria Tushar , Jiang Ziran , Shao Qing , Zou Chen , Albashari Abdullkhaleg Ali , Duan Xingxiang , Ye Qingsong
Published: December 2023

Background

Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro.

Methods

The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection.

Results

DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight.

Conclusions

DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

Graphical Abstract
Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications
Authors: Shi Qingmiao , Chu Qingfei , Zeng Yifan , Yuan Xin , Wang Jinzhi , Zhang Yaqi , Xue Chen , Li Lanjuan
Published: December 2023

RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs). Here, we present an advanced and comprehensive overview of the interplay between methylation modifications and ncRNAs in HCC, with a specific focus on their potential implications for the tumor immune microenvironment. Moreover, we summarize promising therapeutic targets for HCC based on methylation-related proteins. In the future, a more profound investigation is warranted to elucidate the effects of ncRNA methylation modifications on HCC pathogenesis and devise valuable intervention strategies.
Resurgence of syphilis: focusing on emerging clinical strategies and preclinical models
Authors: Xiong Shun , Liu Zhaoping , Zhang Xiaohong , Huang Shaobin , Ding Xuan , Zhou Jie , Yao Jiangchen , Li Weiwei , Liu Shuangquan , Zhao Feijun
Published: December 2023

Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health threat. As such, there has been a great deal of research into clinical strategies for the disease, including diagnostic biomarkers and possible strategies for treatment and prevention. Although serological testing remains the predominant laboratory diagnostic method for syphilis, it is worth noting that investigations pertaining to the DNA of T. pallidum, non-coding RNAs (ncRNAs), chemokines, and metabolites in peripheral blood, cerebrospinal fluid, and other bodily fluids have the potential to offer novel perspectives on the diagnosis of syphilis. In addition, the global spread of antibiotic resistance, such as macrolides and tetracyclines, has posed significant challenges for the treatment of syphilis. Fortunately, there is still no evidence of penicillin resistance. Hence, penicillin is the recommended course of treatment for syphilis, whereas doxycycline, tetracycline, ceftriaxone, and amoxicillin are viable alternative options. In recent years, efforts to discover a vaccine for syphilis have been reignited with better knowledge of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most probable syphilis vaccine candidates. However, research on therapeutic interventions and vaccine development for human subjects is limited due to practical and ethical considerations. Thus, the preclinical model is ideal for conducting research, and it plays an important role in clinical transformation. Different preclinical models have recently emerged, such as in vitro culture and mouse models, which will lay a solid foundation for clinical treatment and prevention of syphilis. This review aims to provide a comprehensive summary of the most recent syphilis tactics, including detection, drug resistance treatments, vaccine development, and preclinical models in clinical practice.
Polystyrene nanobeads exacerbate chronic colitis in mice involving in oxidative stress and hepatic lipid metabolism
Authors: Ma Juan , Wan Yin , Song Lingmin , Wang Luchen , Wang Huimei , Li Yingzhi , Huang Danfei
Published: December 2023

Background

Nanoplastics (NPs) are omnipresent in our lives as a new type of pollution with a tiny size. It can enter organisms from the environment, accumulate in the body, and be passed down the food chain. Inflammatory bowel disease (IBD) is a nonspecific intestinal inflammatory disease that is recurrent and prevalent in the population. Given that the intestinal features of colitis may affect the behavior and toxicity of NPs, it is imperative to clarify the risk and toxicity mechanisms of NPs in colitis models.

Methods and results

In this study, mice were subjected to three cycles of 5-day dextran sulfate sodium (DSS) exposures, with a break of 7 to 11 days between each cycle. After the first cycle of DSS exposure, the mice were fed gavagely with water containing 100 nm polystyrene nanobeads (PS-NPs, at concentrations of 1 mg/kg·BW, 5 mg/kg·BW and 25 mg/kg·BW, respectively) for 28 consecutive days. The results demonstrated that cyclic administration of DSS induced chronic inflammation in mice, while the standard drug “5-aminosalicylic acid (5-ASA)” treatment partially improved colitis manifestations. PS-NPs exacerbated intestinal inflammation in mice with chronic colitis by activating the MAPK signaling pathway. Furthermore, PS-NPs aggravated inflammation, oxidative stress, as well as hepatic lipid metabolism disturbance in the liver of mice with chronic colitis.

Conclusion

PS-NPs exacerbate intestinal inflammation and injury in mice with chronic colitis. This finding highlights chronically ill populations’ susceptibility to environmental hazards, which urgent more research and risk assessment studies.
Inhibition of astroglial hemichannels ameliorates infrasonic noise induced short-term learning and memory impairment
Authors: Zhang Wei , Yin Jue , Gao Bei-Yao , Lu Xi , Duan Ya-Jing , Liu Xu-Yan , Li Ming-Zhen , Jiang Shan
Published: December 2023

As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure.
Morphological aspects and distribution of granules composed of deproteinized bovine bone or human dentin into a putty mixture: an in vitro study
Authors: Pimentel Inês , Henriques Bruno , Silva Filipe , Carvalho Oscar , Teughels Wim , Özcan Mutlu , Souza Júlio C. M.
Published: December 2023

Objective

The main aim of this study was to evaluate the morphological aspects and distribution of granules composed of deproteinized bovine bone mineral (DBBM) and human dentin-derived bone graft (HDBG) into a putty consistency mixture.

Materials and methods

DBBM or HDBG were mixed with an alginate-based hydrogel at two different granule/hydrogel ratio (1:1 and 1:3) and divided into four test groups while two control groups were composed of DBBM or HDBG free of hydrogel. Groups of specimens were cross-sectioned for morphological evaluation by scanning electron microscopy (SEM) at backscattered electrons mode. Details on the dimensions and pores’ size of DBBM and HDBG were evaluated after mixing different amounts of particles and alginate-based hydrogels.

Results

Microscopic analyses revealed a size of DBBM granules ranging from 750 up to 1600 μm while HDBG particles showed particle size ranging from 375 up to 1500 μm. No statistical differences were identified regarding the size of granules (p > 0.5). The mean values of pores’ size of DBBM particles were noticed at around 400 μm while HDBG particles revealed micro-scale pores of around 1–3 μm promoted by the dentin tubules (p < 0.05). The lowest distance between particles was at 125 μm for HDBG and 250 μm for DBBM when the particle content was increased. On decreasing the particles’ content, the distance between particles was larger for DBBM (~ 1000 μm) and HDBG (~ 1100 μm). In fact, statistically significant differences were found when the content of granules increased (p < 0.05).

Conclusions

The increased content of bioactive ceramic granules in a putty consistency mixture with hydrogel decreased the space among granules that can promote a high ceramic density and stimulate the bone growth over the healing process. Macro-scale pores on bovine bone mineral granules stimulate the formation of blood vessels and cell migration while the micro-scale pores of dentin-derived granules are proper for the adsorption of proteins and growth of osteogenic cells on the bone healing process.

Clinical significance

A high amount of bioactive ceramic granules should be considered when mixing with hydrogels as a putty material since that result in small spaces among granules maintaining the bone volume over the bone healing process. Deproteinized bovine bone mineral granules have macro-scale pores providing an enhanced angiogenesis while dentin-derived granules possess only micro-scale pores for the adsorption of proteins and proliferation of osteogenic cells on the bone healing process. Further studies should evaluate the combination of different bioactive ceramic materials for enhanced bone healing.
Acute disc herniation following surgical decompression of lumbar spinal stenosis: a retrospective comparison of mini-open and minimally invasive techniques
Authors: Uri Ofir , Alfandari Liad , Folman Yoram , Keren Amit , Smith William , Paz Inbar , Behrbalk Eyal
Published: December 2023

Background

Disc herniation following decompression of lumbar spinal stenosis is a less familiar surgical complication. Previous studies suggested that open lumbar decompression techniques, associated with relative segmental instability especially in the presence of degenerated disc in older patients, are more likely to result in disc herniation compared to minimally invasive techniques. The current study compares the incidence of acute disc herniation following mini-open and minimally invasive decompression of lumbar spinal stenosis.

Methods

This was a retrospective study reviewing 563 patients who underwent spinal decompression for symptomatic lumbar stenosis by mini-open bilateral partial laminectomy technique or minimally invasive laminotomy utilizing a tubular system. Demographic and clinical data were collected and compared between the groups.

Results

Postoperative disc herniation rate was significantly lower in the minimally invasive group with 2 of 237 cases (0.8%) versus 19 of 326 cases (5.8%) in the mini-open group (p = 0.002). This finding was more noticeable following multi-level procedures with no case of postdecompression disc herniation in the minimally invasive group compared to 8 of 39 cases (20.5%) in the mini-open group (p = 0.003).

Conclusion

The incidence of postoperative disc herniation following spinal decompression for symptomatic lumbar stenosis was 5.8% following mini-open bilateral partial laminectomy compared to only 0.8% after minimally invasive laminotomy (p = 0.002). These findings highlight the more extensive nature of mini-open surgery associated with relative segmental instability that poses a greater risk for postoperative disc herniation.
The first outbreak of African swine fever in Sweden: a survey of pig farmers' perceptions of information received, risks, biosecurity measures and future prospects
Authors: Rajala Elisabeth , Gröndal Hedvig , Sternberg Lewerin Susanna
Published: December 2023

Background

African swine fever (ASF), a viral hemorrhagic disease in domestic pigs and wild boar with up to 100% case fatality, was confirmed in Swedish wild boar in September 2023. The responsible authorities launched a control programme to eradicate the infection. The aim of the current study was to understand (i) how Swedish pig farmers have perceived the information issued by authorities and other stakeholders since the discovery of ASF in wild boar, (ii) which risks they see for introducing the infection to their farm, (iii) what biosecurity measures they have taken on their farms, and (iv) their outlook on the future. Such information is important for evaluating the effectiveness of the early stages of ASF control in Sweden. A questionnaire was designed and distributed to members of the Swedish pig producers’ organisation.

Results

A total of 155 farmers responded to the survey (response rate 36%). Almost all respondents had received general information about ASF (91%, n = 138), and 72% (n = 109) had received information about how they can protect their farm from ASF introduction. A majority (87%, n = 118) thought the information was easy to understand, 90% (n = 137) that is was relevant, and 77% (n = 117) that they currently did not lack any information. If given the resources necessary, 58% (n = 84) of the farmers would like to take additional measures such as fencing, and heavily reduce or eradicate the wild boar population. Wild boars were considered the greatest risk for introduction of ASF into their herd (39%, n = 57), followed by people (30%, n = 44), and transports (16%, n = 23). Many farmers (66%, n = 88) had a positive outlook on the future, and 89% (n = 127) have not changed their plans for the future since the ASF outbreak.

Conclusions

The responding farmers were in general satisfied with the information received in the beginning of the ASF outbreak. The majority have a positive outlook on the future and the outbreak has not caused them to change their plans. Actions that were highlighted as important to safeguard Sweden's pig production included measures to control the wild boar population.
Validation of Oxford nanopore sequencing for improved New World Leishmania species identification via analysis of 70-kDA heat shock protein
Authors: Patiño Luz Helena , Ballesteros Nathalia , Muñoz Marina , Jaimes Jesús , Castillo-Castañeda Adriana C. , Madigan Roy , Paniz-Mondolfi Alberto , Ramírez Juan David
Published: December 2023

Background

Leishmaniasis is a parasitic disease caused by obligate intracellular protozoa of the genus Leishmania. This infection is characterized by a wide range of clinical manifestations, with symptoms greatly dependent on the causal parasitic species. Here we present the design and application of a new 70-kDa heat shock protein gene (hsp70)-based marker of 771 bp (HSP70-Long). We evaluated its sensitivity, specificity and diagnostic performance employing an amplicon-based MinION™ DNA sequencing assay to identify different Leishmania species in clinical samples from humans and reservoirs with cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). We also conducted a comparative analysis between our novel marker and a previously published HSP70 marker known as HSP70-Short, which spans 330 bp.

Methods

A dataset of 27 samples from Colombia, Venezuela and the USA was assembled, of which 26 samples were collected from humans, dogs and cats affected by CL and one sample was collected from a dog with VL in the USA (but originally from Greece). DNA was extracted from each sample and underwent conventional PCR amplification utilizing two distinct HSP70 markers: HSP70-Short and HSP70-Long. The subsequent products were then sequenced using the MinION™ sequencing platform.

Results

The results highlight the distinct characteristics of the newly devised HSP70-Long primer, showcasing the notable specificity of this primer, although its sensitivity is lower than that of the HSP70-Short marker. Notably, both markers demonstrated strong discriminatory capabilities, not only in distinguishing between different species within the Leishmania genus but also in identifying instances of coinfection.

Conclusions

This study underscores the outstanding specificity and effectiveness of HSP70-based MinION™ sequencing, in successfully discriminating between diverse Leishmania species and identifying coinfection events within samples sourced from leishmaniasis cases.

Graphical abstract
In vivo study of newly developed albumin-conjugated urate oxidase for gout treatment
Authors: Cho Jeonghaeng , Yang Byungseop , Lee Jae Hun , Kim Hyunwoo , Kim Hyeongseok , Go Eun Byeol , Bak Dong-ho , Park Su Jin , Kwon Inchan , Choi Jong-il , Lee Kyunghee
Published: December 2023

Background

Exogenously providing engineered Uox with enhanced half-life is one of the important urate-lowering treatments for gout. The potential of PAT101, a recombinant human albumin (rHA)-conjugated variant, was evaluated and compared as a novel gout treatment through various in vivo studies with PAT101 and competing drugs.

Methods

PAT101 was produced by site-specific conjugation of rHA and Aspergillus flavus Uox (AfUox-rHA) through clickable non-natural amino acid (frTet) and Inverse electron demand Diels–Alder (IEDDA) reaction. In vivo pharmacokinetics, efficacy tests and in vitro immunogenetic assay were performed after single or multiple doses of PAT101 and its competitors in BALB/c mice, transgenic (TG) mice, Sprague–Dawley (SD) rats, and non-human primate (NHP).

Results

The half-life of PAT101 in single-dose treated TG mice was more than doubled compared to pegloticase. In SD rats with 4 weeks of repeated administration of rasburicase, only 24% of Uox activity remained, whereas in PAT101, it was maintained by 86%. In the Uox KO model, the survival rate of PAT101 was comparable to that of pegloticase. In addition, human PBMC-based CD4+/CD8+ T-cell activation analysis demonstrated that PAT101 has a lower immune response compared to the original drug, rasburicase.

Conclusion

All results suggest that this rHA-conjugated AfUox, PAT101, can be provided as a reliable source of Uox for gout treatment.
Regulation of telomerase towards tumor therapy
Authors: Yan Siyu , Lin Song , Qiu Hongxin , Wang Xining , He Yijun , Wang Chuanle , Huang Yan
Published: December 2023

Cancer is an aging-related disease, while aging plays an important role in the development process of tumor, thus the two are inextricably associated. Telomere attrition is one of the recognized hallmark events of senescence. Hence, targeting telomerase which could extends telomere sequences to treat tumors is widely favored. Cancer cells rely on high activity of telomerase to maintain a strong proliferative potential. By inhibiting the expression or protein function of telomerase, the growth of cancer cells can be significantly suppressed. In addition, the human immune system itself has a defense system against malignant tumors. However, excessive cell division results in dramatic shortening on telomeres and decline in the function of immune organs that facilitates cancer cell evasion. It has been shown that increasing telomerase activity or telomere length of these immune cells can attenuate senescence, improve cellular viability, and enhance the immunosuppressive microenvironment of tumor. In this paper, we review the telomerase-targeting progress using different anti-tumor strategies from the perspectives of cancer cells and immune cells, respectively, as well as tracking the preclinical and clinical studies of some representative drugs for the prevention or treatment of tumors.
Toward a generalizable machine learning workflow for neurodegenerative disease staging with focus on neurofibrillary tangles
Authors: Vizcarra Juan C. , Pearce Thomas M. , Dugger Brittany N. , Keiser Michael J. , Gearing Marla , Crary John F. , Kiely Evan J. , Morris Meaghan , White Bartholomew , Glass Jonathan D. , Farrell Kurt , Gutman David A.
Published: December 2023

Machine learning (ML) has increasingly been used to assist and expand current practices in neuropathology. However, generating large imaging datasets with quality labels is challenging in fields which demand high levels of expertise. Further complicating matters is the often seen disagreement between experts in neuropathology-related tasks, both at the case level and at a more granular level. Neurofibrillary tangles (NFTs) are a hallmark pathological feature of Alzheimer disease, and are associated with disease progression which warrants further investigation and granular quantification at a scale not currently accessible in routine human assessment. In this work, we first provide a baseline of annotator/rater agreement for the tasks of Braak NFT staging between experts and NFT detection using both experts and novices in neuropathology. We use a whole-slide-image (WSI) cohort of neuropathology cases from Emory University Hospital immunohistochemically stained for Tau. We develop a workflow for gathering annotations of the early stage formation of NFTs (Pre-NFTs) and mature intracellular (iNFTs) and show ML models can be trained to learn annotator nuances for the task of NFT detection in WSIs. We utilize a model-assisted-labeling approach and demonstrate ML models can be used to aid in labeling large datasets efficiently. We also show these models can be used to extract case-level features, which predict Braak NFT stages comparable to expert human raters, and do so at scale. This study provides a generalizable workflow for various pathology and related fields, and also provides a technique for accomplishing a high-level neuropathology task with limited human annotations.
Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain
Authors: Singh Vijay , Menard Marissa A. , Serrano Geidy E. , Beach Thomas G. , Zhao Hien T. , Riley-DiPaolo Alexis , Subrahmanian Nitya , LaVoie Matthew J. , Volpicelli-Daley Laura A.
Published: December 2023

Autosomal dominant pathogenic mutations in Leucine-rich repeat kinase 2 (LRRK2) cause Parkinson’s disease (PD). The most common mutation, G2019S-LRRK2, increases the kinase activity of LRRK2 causing hyper-phosphorylation of its substrates. One of these substrates, Rab10, is phosphorylated at a conserved Thr73 residue (pRab10), and is one of the most abundant LRRK2 Rab GTPases expressed in various tissues. The involvement of Rab10 in neurodegenerative disease, including both PD and Alzheimer’s disease makes pinpointing the cellular and subcellular localization of Rab10 and pRab10 in the brain an important step in understanding its functional role, and how post-translational modifications could impact function. To establish the specificity of antibodies to the phosphorylated form of Rab10 (pRab10), Rab10 specific antisense oligonucleotides were intraventricularly injected into the brains of mice. Further, Rab10 knock out induced neurons, differentiated from human induced pluripotent stem cells were used to test the pRab10 antibody specificity. To amplify the weak immunofluorescence signal of pRab10, tyramide signal amplification was utilized. Rab10 and pRab10 were expressed in the cortex, striatum and the substantia nigra pars compacta. Immunofluorescence for pRab10 was increased in G2019S-LRRK2 knockin mice. Neurons, astrocytes, microglia and oligodendrocytes all showed Rab10 and pRab10 expression. While Rab10 colocalized with endoplasmic reticulum, lysosome and trans-Golgi network markers, pRab10 did not localize to these organelles. However, pRab10, did overlap with markers of the presynaptic terminal in both mouse and human cortex, including α-synuclein. Results from this study suggest Rab10 and pRab10 are expressed in all brain areas and cell types tested in this study, but pRab10 is enriched at the presynaptic terminal. As Rab10 is a LRRK2 kinase substrate, increased kinase activity of G2019S-LRRK2 in PD may affect Rab10 mediated membrane trafficking at the presynaptic terminal in neurons in disease.
Knowledge graph representation method for semantic 3D modeling of Chinese grottoes
Authors: Yang Su , Hou Miaole
Published: December 2023

The integration of 3D geometric models with semantic information significantly improves the applicability and comprehensibility of cultural heritage. The semantic 3D modeling of Chinese grottoes poses challenges for individuals without expertise in cultural heritage due to gaps in domain knowledge and discrepancies in understanding. However, the existing domain ontology and knowledge graph provide an insufficient representation of the knowledge of Chinese grottoes. To overcome these obstacles, we propose a knowledge graph representation method to provide explicit knowledge for participants at different stages of semantic 3D modeling of Chinese grottoes, which includes schema layer construction and data layer construction. On the schema layer, we design a domain ontology named ChgOnto (Chinese Grottoes Ontology) that consists of four high-level concept classes: spatial object, informational object, digital device, and temporal object. Among the classes in the ChgOnto, the components (e.g., cliff wall, cave roof, cliff wall footing), elements (e.g., primary Buddha statue, pedestal, decoration), the properties (e.g., length, width, depth) of caves and niches in Chinese grottoes as well as the spatial relationships between them are all precisely defined. ChgOnto also reuse the classes from the renowned CIDOC CRM ontology in the cultural heritage field and GeoSPARQL in the geospatial domain, facilitating integration between the two subjects. Considering the schema layer as the conceptual data model, the data layer extracts knowledge from unstructured text through natural language processing tools to instantiate the abstract classes and fill the properties of the schema layer. Finally, the knowledge required for semantic 3D modeling of Chinese grottoes is expressed in the data layer by a knowledge graph in a fixed expression form. Dazu Rock Carvings, a World Heritage site in China, is selected as a case study to validate the practicality and effectiveness of the proposed method. The results reveal that our method offers a robust knowledge-sharing platform for the semantic 3D modeling of Chinese grottoes and demonstrates excellent scalability. The method proposed in this paper can also serve as an informative reference for other types of cultural heritage.
Spiral model development of retrofitted robot for tele-operation of conventional hydraulic excavator
Authors: Komatsu Tomohiro , Nagatani Keiji , Hirata Yasuhisa
Published: December 2023

This paper describes the effect of applying spiral model to the development process of robot system for a new entrant company. The robot system was developed to remotely control a conventional hydraulic excavator in order to improve the safety of operators in disaster emergency restoration. The issues of development are the definition of requirements and integration for a practical system in a real environment by a new entrant company. The constraints to the new entry of smaller companies are the following three points. (1) Lack of industry knowledge and data to define requirements (2) Lack of on-site environment and machinery for investigation and testing (3) Lack of experience in robot development To solve the problems under these constraints, the spiral model divides the development based on the prototype into 4-steps, and repeats this series of processes. This method was applied to clarify the necessary functions and performance of the robot step by step, and to construct a system with robustness in a real environment. As a result, this robot system has been successfully utilized in emergency disaster recovery tasks due to landslides, and removing debris in the Fukushima Daiichi Nuclear Power Plant, reducing the mental and physical burden on the operators.
Diaphragmatic dysfunction in hemodialysis patients: risk factors and effect of incentive spirometry training
Authors: Ahmed Laila Abdel Naby , Eltrawy Heba H. , Elsadek Amira Mohamed , Ali Wagenat E. , Abozeid Hanaa Elsayed , Qutb Sanaa Fathy , Elsayed Fatma Gamal , Enayet Alshimaa A. Ezzat M. , Elshehawy Ahmed A.
Published: December 2023

Background

Diaphragmatic dysfunction (DD) in hemodialysis patients is a scarcely studied issue. Incentive spirometry (IS) is a commonly prescribed maneuver used to prevent or manage pulmonary complications. The present study aimed to identify the prevalence and risk factors of DD in 100 HD patients. Moreover, we assessed the role of IS in management of DD in those patients.

Methods

The present study followed a hybrid design with two phases. In the first cross-sectional phase, 100 consecutive maintenance HD patients for at least 3 years were evaluated for the presence of DD using ultrasound. In the second interventional phase, patients with DD (n = 43) were randomly assigned to receive IS (n = 22) or standard care (n = 21) for management of DD.

Results

Comparison between patients with DD and patients without regarding clinical and laboratory data revealed that the former group had significantly higher frequency of males [29 (67.4%)/14 (32.6%) vs. 26 (45.6%)/31 (54.4%), p = 0.03] with lower BMI [23.8 ± 3.8 vs. 26.3 ± 3.5 kg/m2, p < 0.001] and longer HD duration (82.2 ± 42.1 vs. 64.8 ± 36.9 months, p = 0.031). Moreover, it was noted that DD group had significantly higher frequency of patients with moderate/severe malnutrition (81.4% vs. 45.6%, p = 0.005), lower Hb levels (9.6 ± 1.5 vs. 10.3 ± 1.4 gm/dL, p = 0.011), lower albumin levels (3.4 ± 0.4 vs. 4.1 ± 0.5 gm/dL, p < 0.001) and higher hsCRP levels [median (IQR) 113.6 (90.9–130.4) vs. 91.1 (50.9–105.6) mg/dL, p < 0.001] as compared to patients without DD. While no significant differences were found between patients receiving study interventions at baseline, patients submitted to IS training showed significant improvement of diaphragmatic excursion measurements as compared to the standard care group.

Conclusions

In conclusion, DD is commonly encountered in HD patients. Probable risk factors include longer HD duration and low albumin levels. Use of IS can improve diaphragmatic excursion in affected patients.
Intention to receive the monkeypox vaccine and its psychological and sociodemographic predictors: a cross-sectional survey in the general population of Peru
Authors: Caycho-Rodríguez Tomás , Valencia Pablo D. , Ventura-León José , Carbajal-León Carlos , Vilca Lindsey W. , Gallegos Miguel , Reyes-Bossio Mario , Noe-Grijalva Martin , Delgado-Campusano Mariel , del Carpio Toia Águeda Muñoz , Torales Julio , Barria-Asenjo Nicol A.
Published: December 2023

Objective

The objective of this study was to identify predictors of intention to be vaccinated against Monkeypox (Mpox) in a sample of Peruvian citizens. 

Methods

A set of sociodemographic and psychological predictors were used, such as sex, sexual orientation, educational level, previous diagnosis of COVID-19, marital status, complete vaccination against COVID-19, employment status, living with vulnerable people, presence of chronic disease, area of residence, perceived usefulness of COVID-19 vaccines, fear of Mpox, conspiracy beliefs about Mpox, among others.

A total of 472 Peruvian adults participated, selected by non-probabilistic snowball convenience sampling. A sociodemographic survey, the Mpox Fear Scale, was used. Conspiracy Beliefs about Mpox was assessed using three questions created specifically for this study. For inferential purposes, simple ordinal regressions ("crude models") were performed between each factor and the outcome. 

Results

Regarding their intention to be vaccinated against Mpox, more than 60% expressed clear approval. Being non-heterosexual, having greater emotional fear of Mpox, and perceiving some potential for this disease to become the next pandemic were related to greater intention to vaccinate. On the other hand, being older, having low perceived usefulness of COVID-19 vaccines, and having higher conspiracy beliefs about Mpox were associated with lower intention to vaccinate. 

Conclusion

The study provides initial information for future research seeking to better analyze Mpox vaccination intention. In addition, cross-sectional data are provided that can be used to develop public health policies that target subgroups with low prevalence of intention to vaccinate against Mpox.
A False Flag
Authors: Masco Joseph
Published: December 2023

This chapter argues that false accusations of conspiracy in pursuit of antidemocratic goals is an increasingly normalized form of politics. It examines narrative techniques for flattening out politics, focusing on those which work to promote affective recruitment and polarization rather than critical reflection. Given the prevalence of deceptions and false flag operations in a mass mediated age, the chapter calls for a reconsideration of conspiratorial thought as a necessary survival tool in contemporary life. Focusing on official US national security deceptions over the past half century, the chapter ultimately theorized the role of political demonology and deception as illiberal political tools that threaten democratic thought and collective action.