bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden of disease - A population-based study
Authors: Sevin Caroline , Hatteb Samira , Clément Aurore , Bignami Fabrizia , Chillotti Louis , Bugnard Françoise , Bénard Stève , Boespflug-Tanguy Odile
Published: August 2023

Background

X-linked adrenoleukodystrophy (ALD) is a rare metabolic and neurodegenerative disorder belonging to the group of leukodystrophies, with an estimated incidence around 1:25 000 newborns worldwide, mostly among men. Childhood Cerebral ALD (CCALD) is the most severe form with a poor prognosis if not properly treated during the first years of life. Currently, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely available for CCALD treatment. To date, there is a lack of data regarding CCALD epidemiology, natural history, and current management in France. This knowledge is crucial for the development of new therapies such as gene therapies. In this context, the French National Health Data System (SNDS) is a particularly indicated database to collect information meeting these needs. A non-interventional, national, real-life, retrospective study was performed using secondary data from the national ALD registry (LEUKOFRANCE) and SNDS. CCALD patients detected between 2009 and 2018 and successfully matched between LEUKOFRANCE and SNDS were included in this study. Index date was defined as the first CCALD event detected during study period. Subgroups of patients with sufficient follow-up (6 months) and history (1 year) available around index date were analyzed to assess CCALD burden and natural history.

Results

52 patients were included into the matched cohort. Median annual incidence of CCALD was estimated at 4 patients. Median age at CCALD diagnosis was 7.0 years. Among patients without allo-HSCT, five-year overall survival was 66.6%, with 93.3% of them presenting at least one CCALD symptom and 62.1% presenting a least one major functional disability (MFD). Among patients with allo-HSCT, five-year overall survival was 94.4%, with only 11.1% of patients presenting CCALD symptoms, and 16.7% of presenting a MFD. Mean annualized costs were almost twice as important among patients without allo-HSCT, with 49,211€, 23,117€, respectively. Costs were almost exclusively represented by hospitalizations.

Conclusions

To the best of our knowledge, this is the most up to date study analyzing CCALD epidemiology, clinical and economic burden in France. The necessity of a precocious management with HSCT highlight the potential benefits of including an expanded screening program among newborns, coupled with family screenings when a mutation is detected.
Physicians’ use and perceptions of genetic testing for rare diseases in China: a nationwide cross-sectional study
Authors: Liu Weida , Liu Peng , Guo Dan , Jin Ye , Zhao Kun , Zheng Jiayin , Li Kexin , Li Linkang , Zhang Shuyang
Published: August 2023

Background

Genetic testing can facilitate the diagnosis and subsequent therapeutic management of rare diseases. However, there is a lack of data on the use of genetic testing for rare diseases. This study aims to describe the utilization rate and troubles encountered by clinicians in treating rare diseases with genetic testing.

Methods

A cross-sectional electronic questionnaire survey was conducted between June and October 2022 among the medical staff from the hospitals covering all provinces, municipalities, and autonomous regions of China. The survey on genetic testing focused on whether genetic testing was used in the diagnosis and treatment of rare diseases, the specific methods of genetic testing, and the problems encountered when using genetic testing.

Results

A total of 20,132 physicians who had treated rare diseases were included, of whom 35.5% were from the central region, 36.7% were from the eastern region, and 27.8% were from the western region. The total utilization rate of genetic testing for rare diseases was 76.0% (95%CI: 75.4–76.6). The use of genetic testing was highest in the Eastern region (79.2% [95% CI: 78.3–80.1]), followed by the Central (75.9% [95% CI: 74.9–76.9]) and Western regions (71.9% [95% CI: 70.7–73.1]). More than 90% (94.1% [95%CI: 93.4–94.8]) of pediatricians had used genetic testing to treat rare diseases, with surgeons having the lowest use of genetic testing (58.3% [95% CI: 56.6–60.0]). Physicians’ departments and education levels affect the use of genetic testing. Most physicians have used a variety of genetic tests in the management of rare diseases, the most popular methods were “Whole-exome sequencing (Proband)” and “Whole-exome sequencing (families of three or more)”. Doctors have encountered many problems with the use of genetic testing in the diagnosis and treatment of rare diseases, among which the high price was the main concern of medical workers.

Conclusion

Three-quarters of physicians used genetic testing in rare disease practice, and there were regional differences in the use of genetic testing. Recognition of the utilization of genetic testing can help identify patterns of resource utilization in different regions and provide a more comprehensive picture of the epidemiology of rare diseases in jurisdictions.
Adult mortality patterns in Yemen before and during armed conflict: evidence from a web survey of the global diaspora
Authors: McGowan Catherine R. , Alhaffar Mervat , Ekoriko Promise , Al-Refai Sawsan , Badr Jamal , Bell Lucy , Checchi Francesco
Published: August 2023

Background

The ongoing war in Yemen has created a severe and protracted crisis that has left nearly three-quarters of the population in need of urgent humanitarian assistance. Despite eight years of conflict there exist few robust estimates of how the conflict (and the conflict combined with the COVID-19 pandemic) have affected mortality in Yemen. As the security situation has limited access to affected populations we have designed a novel alternative to local mortality surveys.

Methods

We used a web-based, respondent-driven sampling method to disseminate a mortality survey amongst the global Yemeni diaspora. We used Cox proportional hazards survival models to estimate the association between the exposure (i.e. between the pre-conflict, conflict, and conflict/pandemic periods) and mortality risk, adjusted for gender and birth cohort.

Results

Eighty-nine eligible respondents completed the survey. Respondents provided data on the status of 1704 individuals of whom 85 (5%) had died; of these 65 (3.8%) were reported to have died in Yemen. An analysis of survivorship of respondents’ parents after their 50th birthday (adjusted for gender and birth cohort) provided weak evidence that the war and pandemic periods were associated with higher mortality when compared to the pre-war period. Analysis of the subset of individuals who died in Yemen also suggested an increased, but non-significant hazard of dying during the war/pandemic period: this association tended towards significance when allowing for varying degrees of out-migration from Yemen across the cohort. The number of deaths amongst respondents’ siblings and children under five in Yemen were too low to allow meaningful analysis.

Conclusions

Our data suggest increased mortality during the war/pandemic period, compared to the pre-war period, among older Yemeni adults. However, our findings require careful interpretation as our study design cannot establish causation, and as our small and non-representative sample appeared skewed towards higher-income, urban communities. Surveys of diaspora populations offer a promising means of describing mortality patterns in crisis-affected populations; though, large numbers of respondents are likely required to achieve accurate mortality estimates and to adjust for selection bias.
Mother–child interactions in adolescents with borderline personality disorder traits and the impact of early life maltreatment
Authors: Williams Katharina , Fleck Leonie , Fuchs Anna , Koenig Julian , Kaess Michael
Published: August 2023

Background

Early detection and intervention of borderline personality disorder (BPD) in adolescence has become a public health priority. Theoretical models emphasize the role of social interactions and transgenerational mechanisms in the development of the disorder suggesting a closer look at caregiver-child relationships.

Methods

The current study investigated mother-adolescent interactions and their association with adolescent BPD traits by using a case–control design. Thirty-eight adolescent patients with ≥ 3 BPD traits and their mothers (BPD-G) were investigated in contrast to 35 healthy control dyads (HC-G). Maternal, adolescent and dyadic behavior was coded using the Coding Interactive Behavior Manual (CIB) during two interactions: a fun day planning and a stress paradigm. Additional effects of maternal and/or adolescent early life maltreatment (ELM) on behavior were also explored.

Results

BPD-G displayed a significantly lower quality of maternal, adolescent and dyadic behavior than the HC-G during both interactions. Maternal and adolescent behavior was predicted by BPD traits alone, whilst dyadic behavior was also influenced by general adolescent psychopathology. Exploratory analyses of CIB subscales showed that whilst HC-G increased their reciprocal behavior during stress compared to the fun day planning, BPD-G dyads decreased it. Maternal ELM did not differ between groups or have any effect on behavior. Adolescent ELM was correlated with behavioral outcome variables, but did not explain behavioral outcomes above and beyond the effect of clinical status.

Discussion/Conclusion

Our data suggest a stronger focus on parent–child interactions in BPD-specific therapies to enhance long-term treatment outcomes in adolescent BPD patients. Further research employing study designs that allow the analyses of bidirectional transactions (e.g. longitudinal design, behavioral microcoding) is needed.
CIS deletion by CRISPR/Cas9 enhances human primary natural killer cell functions against allogeneic glioblastoma
Authors: Nakazawa Tsutomu , Morimoto Takayuki , Maeoka Ryosuke , Matsuda Ryosuke , Nakamura Mitsutoshi , Nishimura Fumihiko , Ouji Noriko , Yamada Shuichi , Nakagawa Ichiro , Park Young Soo , Ito Toshihiro , Nakase Hiroyuki , Tsujimura Takahiro
Published: August 2023

Background

Glioblastoma (GBM) is the most common malignant brain tumor and has “immunologically cold” features. Changing GBM to an “immunologically hot” tumor requires a strong trigger that induces initial immune responses in GBM. Allogeneic natural killer cells (NKCs) have gained considerable attention as promising immunotherapeutic tools against cancer, where gene-edited NKCs would result in effective anti-cancer treatment. The present study focused on the immune checkpoint molecule cytokine-inducible SH2-containing protein (CISH, or CIS) as a critical negative regulator in NKCs.

Methods

The GBM tumor environment featured with immunological aspect was analyzed with Cancer immunogram and GlioVis. We generated human primary CIS-deleted NKCs (NK dCIS) using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting genome sites on CIS coding exons. The genome-edited NKCs underwent microarray with differential expression analysis and gene set enrichment analysis (GSEA). The anti-GBM activity of the genome-edited NKCs was evaluated by apoptosis induction effects against allogeneic GBM cells and spheroids. We further detected in vivo antitumor effects using xenograft brain tumor mice.

Results

We successfully induced human CIS-deleted NKCs (NK dCIS) by combining our specific human NKC expansion method available for clinical application and genome editing technology. CIS gene-specific guide RNA/Cas9 protein complex suppressed CIS expression in the expanded NKCs with high expansion efficacy. Comprehensive gene expression analysis demonstrated increased expression of 265 genes and decreased expression of 86 genes in the NK dCIS. Gene set enrichment analysis revealed that the enriched genes were involved in NKC effector functions. Functional analysis revealed that the NK dCIS had increased interferon (IFN)ɤ and tumor necrosis factor (TNF) production. CIS deletion enhanced NKC-mediated apoptosis induction against allogeneic GBM cells and spheroids. Intracranial administration of the allogeneic NKCs prolonged the overall survival of xenograft brain tumor mice. Furthermore, the NK dCIS extended the overall survival of the mice.

Conclusion

The findings demonstrated the successful induction of human primary NK dCIS with CRISPR/Cas9 with efficient expansion. CIS deletion enhanced the NKC-mediated anti-tumor effects in allogeneic GBM and could be a promising immunotherapeutic alternative for patients with GBM.
AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer
Authors: Yin Linglong , Ye Yubing , Zou Ling , Lin Jinli , Dai Yi , Fu Yongming , Liu Youhong , Peng Yuchong , Gao Yingxue , Fu Yuxin , Qi Xuli , Deng Tanggang , Zhang Songwei , Li Xiong
Published: August 2023

Background

Prostate cancer(PCa) is the most commonly occurring male cancer in the USA. Abiraterone or Enzalutamide have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). However, the treatment-emergent neuroendocrine PCa (t-NEPC) may develop, resulting in drug resistance in about 10–17% CRPC patients. The detailed mechanisms remain unclear..

Methods

The expression correlation of TOMM20 and AR in PCa was determined by analyzing publicly available datasets, or by IHC staining in tumor specimens. The protein interaction of TOMM20 and AR was validated by co-immunoprecipitation or GST pull-down assay. The impact of TOMM20 depletion on drug sensitivity were elucidated by assays of cell proliferation, invasion, sphere formation, xenograft growth and intravenous metastasis. The intracellular ROS level was measured by flow cytometry, and the NEPC transdifferentiation and characteristics of cancer stem-like cells were validated by RNA-seq, RT-PCR and western blotting.

Results

The protein level of TOMM20 is positively correlated with AR in PCa cells and specimens. TOMM20 protein physically interacts with AR. AR antagonists induced the protein degradation of TOMM20 through autophagy-lysosomal pathway, thereby elevating the intracellular ROS level and activating PI3K/AKT signaling pathway. When TOMM20 was depleted, PCa cells underwent EMT, acquired the characteristics of cancer stem-like cells, and developed resistance to AR antagonists. The stable depletion of TOMM20 promoted the transdifferentiation of PCa adenocarcinoma into NEPC and metastasis. Conversely, the rescue of TOMM20 re-sensitized the resistant PCa cells to AR antagonists.

Conclusions

TOMM20 protein degradation induced by AR antagonists promoted the transdifferentiation of PCa to NEPC, thereby revealing a novel molecular mechanism by which AR antagonists develop drug resistance through mitochondrial outer membrane-mediated signaling pathway. These findings suggested that the decreasing or loss of TOMM20 expression in PCa tissues might become a useful predictor of PCa resistance to AR antagonists.
The CUT&RUN suspect list of problematic regions of the genome
Authors: Nordin Anna , Zambanini Gianluca , Pagella Pierfrancesco , Cantù Claudio
Published: August 2023

Background

Cleavage Under Targets and Release Using Nuclease (CUT&RUN) is an increasingly popular technique to map genome-wide binding profiles of histone modifications, transcription factors, and co-factors. The ENCODE project and others have compiled blacklists for ChIP-seq which have been widely adopted: these lists contain regions of high and unstructured signal, regardless of cell type or protein target, indicating that these are false positives. While CUT&RUN obtains similar results to ChIP-seq, its biochemistry and subsequent data analyses are different. We found that this results in a CUT&RUN-specific set of undesired high-signal regions.

Results

We compile suspect lists based on CUT&RUN data for the human and mouse genomes, identifying regions consistently called as peaks in negative controls. Using published CUT&RUN data from our and other labs, we show that the CUT&RUN suspect regions can persist even when peak calling is performed with SEACR or MACS2 against a negative control and after ENCODE blacklist removal. Moreover, we experimentally validate the CUT&RUN suspect lists by performing reiterative negative control experiments in which no specific protein is targeted, showing that they capture more than 80% of the peaks identified.

Conclusions

We propose that removing these problematic regions can substantially improve peak calling in CUT&RUN experiments, resulting in more reliable datasets.
Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial
Authors: McMahon Amy , Kaptoge Stephen , Walker Matthew , Mehenny Susan , Gilchrist Philippe T , Sambrook Jennifer , Akhtar Naim , Sweeting Michael , Wood Angela M , Stirrups Kathleen , Chung Ryan , Fahle Sarah , Johnson Elisha , Cullen Donna , Godfrey Rosemary , Duthie Shannon , Allen Louise , Harvey Paul , Berkson Michael , Allen Elizabeth , Watkins Nicholas A , Bradley John R , Kingston Nathalie , Miflin Gail , Armitage Jane , Roberts David J , Danesh John , Di Angelantonio Emanuele
Published: August 2023

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (“cluster”) has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT’s current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.
The recent introduction of Angiostrongylus cantonensis and its intermediate host Achatina fulica into Guadeloupe detected by phylogenetic analyses
Authors: Gamiette Gelixa , Ferdinand Séverine , Couvin David , Dard Céline , Talarmin Antoine
Published: August 2023

Background

Angiostrongylus cantonensis (rat lungworm) is the main pathogen responsible for eosinophilic meningitis in humans. One of its intermediate snail hosts, Achatina fulica, was already present in many countries around the world before it appeared in the West Indies in the late 1980s. In the French territories in the Caribbean and northern South America, the first cases of human neuroangiostrongyliasis were reported in Martinique, Guadeloupe and French Guiana in 2002, 2013 and 2017, respectively. In order to better characterize angiostrongyliasis in Guadeloupe, particularly its geographical origin and route of introduction, we undertook molecular characterization of adult worms of Angiostrongylus cantonensis and its intermediate host Achatina fulica.

Methods

Genomic DNA of adult Angiostrongylus cantonensis and Achatina fulica was extracted and amplified by polymerase chain reaction (PCR) targeting the mitochondrial genes cytochrome B and C for A. cantonensis and 16S ribosomal RNA for A. fulica. The PCR products were sequenced and studied by phylogenetic analysis.

Results

Cytochrome B and cytochrome C molecular markers indicate a monophyletic lineage of A. cantonensis adult worms in Guadeloupe. Two sequences of A. fulica were identified.

Conclusions

These results confirm the recent introduction of both Angiostrongylus cantonensis and Achatina fulica into Guadeloupe. Achatina fulica in Guadeloupe shares a common origin with those in Barbados and New Caledonia, while Angiostrongylus cantonensis in Guadeloupe shares a common origin with those in Brazil, Hawaii and Japan.

Graphical Abstract
The effects of alteration in muscle activation on the iliotibial band during an exhaustive run
Authors: Chen Shane Fei , Wang Yan , Bing Fangbo , Zhang Ming
Published: August 2023

Purpose

Long exhausted running causes pain at the lateral femoral epicondyle for some runners. The pain has been revealed to be related to the behavior of the iliotibial band (ITB) during running. The purpose of this study is to examine the effects of in-series musculature on the behavior of the ITB in healthy participants during an exhaustive run.

Methods

Twenty-five healthy participants (15 males, 10 females) were recruited in the current study. All participants performed a 30-minute exhaustive run at a self-selected speed with laboratory-provided footwear. Muscle activities of ITB-related muscles including tensor fascia latae (TFL), gluteus maximus (Gmax), gluteus medius (Gmed), biceps femoris (BF), and vastus lateralis (VL) were recorded using surface electromyography (EMG).

Results

Maximum amplitudes at the initial stage (the first minute), the mid stage (the 15-minute), and the end stage (the 30-minute) were compared during the exhaustive running. Significant decreases (p < 0.05) were observed in the maximum amplitudes of the TFL, Gmax, Gmed, and BF at the mid (decreased by ~ 15%) and end (decreased by ~ 30%) stages compared to the initial stage. The onset and the offset remained unaltered during the running (p ≥ 0.05).

Conclusion

The behavior of the healthy ITB might be altered due to the activities of the in-series musculature. Excessive compression forces might be applied to the lateral femoral epicondyle from the ITB to provide stability for the knee joint during an exhaustive run. The findings could provide a basic understanding of the behavior of healthy ITB.
On the basis of sex: male vs. female rat adenosine A1/A2A receptor affinity
Authors: Janse van Rensburg Helena D. , Terre’Blanche Gisella , Van der Walt Mietha M.
Published: August 2023

Objective

To ensure reproducibility in biomedical research, the biological variable sex must be reported; yet a reason for using male (instead of female) rodents is seldom given. In our search for novel adenosine receptor ligands, our research group routinely determines a test compound’s binding affinities at male Sprague-Dawley rat (r) adenosine A1 and A2A receptors via in vitro radioligand binding studies. This pilot study compared the binding affinities of four adenosine receptor ligands (frequently used as reference standards) at male and female adenosine rA1 and rA2A receptors.

Results

The inhibition constant (Ki) values determined using female rats correspond well to the values obtained using male rats and no markable difference could be observed in affinity and selectivity of reference standards. For example, DPCPX the selective adenosine A1 receptor antagonist: male rA1Ki: 0.5 ± 0.1 nM versus female rA1Ki: 0.5 ± 0.03 nM; male rA2AKi: 149 ± 23 nM versus female rA2AKi: 135 ± 29 nM. From the limited data at hand, we conclude that even when using female rats for in vitro studies without regard for the oestrous cycle, the obtained data did not vary much from their male counterparts.
Tumor-derived interleukin-1 receptor antagonist exhibits immunosuppressive functions and promotes pancreatic cancer
Authors: Fan Yu-Ching , Fong Yu-Cin , Kuo Chun-Tse , Li Chia-Wei , Chen Wei-Yu , Lin Jian-Da , Bürtin Florian , Linnebacher Michael , Bui Quoc Thang , Lee Kuan-Der , Tsai Yuan-Chin
Published: August 2023

Background

Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory cytokine; however, its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research, we investigated the role and mechanism of IL-1Ra in malignant progression of PDA.

Results

Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples, we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors, we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene, encoding IL-1Ra, and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice, highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently, we found an increase in CD8+ T cells and a decrease in CD11b+Ly6G− immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells, we utilized a luciferase-based reporter CD4+ T cell line and splenocytes, which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8+ T cells, and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes.

Conclusions

Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra, and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of PDA.
Experiences of a virtual day program for adolescents with eating disorders: a qualitative analysis of benefits and barriers
Authors: Catenacci Vanessa , Couturier Jennifer
Published: August 2023

Background

Throughout the COVID-19 pandemic, there was a detrimental impact to the symptoms and treatment of eating disorders, causing an increase in medical admissions and visits. Day treatment programs (DTPs), often used to bridge the gap between inpatient and outpatient treatment, were converted to online formats. This study aims to explore the impact of the transition to virtual DTPs on eating disorder treatment from the perspective of adolescents, their caregivers, and program staff.

Methods

Twelve participants (3 adolescents, 4 caregivers, 5 healthcare providers) in a virtual day treatment program were interviewed using a semi-structured interview guide. Interviews were transcribed and managed with qualitative software NVivo 11.0. Conventional analysis was used to inductively identify pertinent themes related to patient, caregiver, and healthcare staff perceptions and experiences of the virtual day treatment. Summative content analysis provided counts of the barriers and benefits of virtual day treatment as identified by participants.

Results

The majority of participants (10/12) had exposure to both virtual and in person settings, most participants (11/12) felt in-person day programs would be superior to virtual programs. Common limitations of the virtual format were feelings of isolation, less support from healthcare providers, parental burnout, and increased disordered eating. Common benefits were increased accessibility, parental involvement, improved communication with healthcare staff, and the ability for participants to be in their home environment and eat home food. Suggestions for improvement included designing a hybrid model of day treatment, increased family involvement, extending the day program to include dinners with family, and screening for patient appropriateness for the virtual setting.

Conclusion

This qualitative study suggests that there are many barriers to effective implementation of virtual day programs. However, the virtual DTP program offers increased accessibility to patients during a period of a health pandemic and to patients in rural/remote areas with limited treatment options. Suggestions provided by participants in this study, such as increased family involvement, frequency of in person check-ins and increased number of meals supported by the program, may help to improve outcomes in virtual day treatment programs.
Berberine-loaded albumin nanoparticles reverse aflatoxin B1-induced liver hyperplasia
Authors: Khedr Sarah M. , Ghareeb Doaa A. , Fathy Shadia A. , Hamdy Germine M.
Published: August 2023

Hepatocellular carcinoma (HCC) can be produced from aflatoxin B1 (AFB1) administration. Although berberine (BER) acts as an anticancer agent and can counteract the AFB1 effect, it has low bioavailability. Nanotechnology can overcome this problem. This research aimed to synthesize berberine nanoparticles (NPs) and then estimate their therapeutic effect compared to that of berberine against aflatoxin-induced hepatotoxicity. The desolvation method was used to prepare BER–NPs. Aflatoxicosis was induced by 5 consecutive intraperitoneal injections (IP) of 200 µg/kg/day AFB dissolved in dimethylsulfoxide (DMSO). After the induction period, two treatments were performed: the first with 100 mg/kg BER and the second with 10 mg/kg BER-NPs. Liver, kidney, and diabetic profiles were estimated by using standardized methods. Hepatic oxidative stress, inflammatory, cancer cell proliferation, and invasion markers were used by ELISA and qPCR techniques. The TEM image shows that both BSA NPs and BER-BSA NPs had spherical, regular, and uniform shapes. The BER encapsulation efficiency % was 78.5. The formed-BER-BSA NPs showed a loading capacity % of 7.71 and the synthesis yield % of 92.6. AFB1 increases pro-oxidant markers, decreases antioxidant systems, stimulates inflammatory enzymes, inhibits anti-inflammatory markers, decreases tumor suppressor enzymes, increases oncogenes, increases glycolytic activity, prevents cell death, and promotes cell growth. Most of the biochemical markers and hepatic architecture were normalized in the BER-BSA NP-treated group but not in the BER-treated group. Altogether, the obtained data proved that treatment with BER-NPs was more efficient than treatment with berberine against aflatoxicoses induced in rats.
But aren’t all soaps metal soaps? A review of applications, physico-chemical properties of metal soaps and their occurrence in cultural heritage studies
Authors: Russo Silvia , Brambilla Laura , Thomas Jean Baptiste , Joseph Edith
Published: August 2023

Metal soaps, the organic salts resulting from the interaction of fatty acids and metal cations, arouse interest in the scientific field because of their versatility in a great range of chemical applications as well as because of the mechanism of their formation during degradation processes. This article presents a review of the synthetic pathways used to produce metal soaps, their relevant physico-chemical properties, and how these reflect in their applications. Common industrial uses of metal soaps are reported, with a particular focus on those applications, such as cosmetics, paints, and coatings, that have an impact on the cultural heritage field. In addition, the occurrence of metal soaps in cultural heritage studies is presented, ranging from archaeological and ethnographic artefacts to fine art objects, and discussed per class of materials. An overview of the presence or absence of metal soaps in historical artefacts due to the interaction of metal parts or mineral pigments with fatty acids is given herein. This collection shows a variety of situations in which metal soaps—particularly lead, zinc and copper soaps—can form on composite objects made of different materials such as wood, leather and fatty-acid-containing materials (e.g., waxes), in the presence of metal, metal alloys or pigments.
PTS and PTSO, two organosulfur compounds from onion by-products as a novel solution for plant disease and pest management
Authors: Falcón-Piñeiro Ana , García-López David , Gil-Martínez Lidia , de la Torre José M. , Carmona-Yañez María Dolores , Katalayi-Muleli Antoine , Guillamón Enrique , Barrero-Domínguez Belén , López-Feria Silvia , Garrido Dolores , Baños Alberto
Published: August 2023

Background

Over the past decade, the great impact of agricultural crop diseases has generated considerable economic losses and has compromised the production of edible crops at a time when the world population is only expected to rise, leading to the search for new pest management strategies. Besides that, the environmental impact resulting from the continued use of chemical pesticides has led to the search for natural and sustainable alternatives. One of the existing solutions that currently stands out for its effectiveness is the use of bioactive plant extracts. This study aims to evaluate the antimicrobial activity of propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO), two organosulfur compounds (OSCs) derived fromAllium cepa, against a wide range of target bacteria and fungi. To this end, various in vitro procedures were conducted as well as soil sanitization tests using sterile substrate inoculated with soil-borne pathogens. In addition, this study also evaluates the pesticidal activity of both compounds through in vitro mortality and repellence tests.

Results

PTS and PTSO revealed inhibition activity on all the pathogens tested, belonging to different taxonomic groups. Moreover, both significatively reduced the population of bacteria and fungi in soil. The quantification of active substances in soil carried out in parallel to the microbial quantification showed that their use reduces the risk of residue accumulation since they break down quickly when applied. The set of antimicrobial tests performed demonstrated that the antifungal effect of both compounds is higher than the bactericidal effect. Lastly, PTS and PTSO showed a concentration-dependent significant biocidal and repellent effect against aphids.

Conclusions

The results presented in this work demonstrate that both PTS and PTSO have a significant antimicrobial and pesticidal activity against the great majority of phytopathogens tested, being a promising tool to improve pest management in crops.

Graphical Abstract
Ag+ colorimetric sensor based on graphene oxide/nano-platinum composite
Authors: Qu Yanping , Yakub Ibrahim , Baini Rubiyah , Hu WenShuo , Wang Lizhen
Published: August 2023

With the development of society, pollution accidents occur more frequently, and the effects of toxic substances containing silver on human health and environment are increasingly extensive. Therefore, the real-time on-site monitoring of silver ions is urgently needed. Based on the catalase-like properties of graphene/nano-platinum composites and the coupling effect between Pt and Ag+, a simple, unlabeled colorimetric sensing method is proposed to achieve the quantitative detection of Ag+. Under optimal conditions, the detection range of Ag+ by this colorimetric sensing method is 0.5–1000 μM, and the detection limit is 0.5 μM, which is lower than the previously reported detection limit of unlabeled Ag+ colorimetric sensing method, showing higher sensitivity and detection range. Under the same conditions, the sensor has almost no response to interference ions, showing good specific recognition ability. In addition, the colorimetric sensing method can be used to detect Ag+ in actual water samples, serving as a new paradigm for visual detection of Ag+.

Graphical abstract
Possible high risk of transmission of the Nipah virus in South and South East Asia: a review
Authors: Joshi Jagadish , Shah Yogendra , Pandey Kishor , Ojha Ram Prashad , Joshi Chet Raj , Bhatt Lok Raj , Dumre Shyam Prakash , Acharya Pushpa Raj , Joshi Hem Raj , Rimal Shikha , Shahi Ramesh , Pokharel Deepak , Khadka Kamal Singh , Dahal Bimal , Nepal Saroj , Dhami Ram Singh , Pant Krishna Prasad , Basnet Rajdip , Pandey Basu Dev
Published: August 2023

Nipah virus (NiV) is a zoonotic, single-stranded RNA virus from the family Paramyxoviridae, genus Henipavirus. NiV is a biosafety-level-4 pathogen that is mostly spread by Pteropus species, which serve as its natural reservoir host. NiV is one of the major public health challenges in South and South East Asia. However, few molecular studies have been conducted to characterise NiV in a specific region. The main objective of this review is to understand the epidemiology, pathogenesis, molecular surveillance, transmission dynamics, genetic diversity, reservoir host, clinical characteristics, and phylogenetics of NiV. South and South East Asian nations have experienced NiV outbreaks. Phylogenetic analysis confirmed that two primary clades of NiV are in circulation. In humans, NiV causes severe respiratory illness and/or deadly encephalitis. NiV is mainly diagnosed by ELISA along with PCR. Therefore, we recommend that the governments of the region support the One Health approach to reducing the risk of zoonotic disease transmission in their respective countries.
New fly records of potential biological control importance in Saudi Arabia (order Diptera)
Authors: El-Hawagry Magdi , Soliman Ahmed M. , Abdel-Dayem Mahmoud S. , Al Dhafer Hathal M.
Published: August 2023

Background

The Ministry of Environment, Water and Agriculture in Saudi Arabia has begun funding some projects to set up some agricultural pest control programs. Therefore, it is very important to enumerate all the predacious or parasitic insects that live on or in other agricultural insect pests and have the potential to become biological control agents against these pests.

Results

In the present study, nine fly species of potential importance in biological pest control are recorded for the first time from Saudi Arabia, namely, Spogostylum ventrale Bezzi, 1924, Prothaplocnemis anthracina (Becker, 1902) [family Bombyliidae], Alloxytropus anomalus Bezzi, 1925, Scenopinus minusculus (Séguy, 1934) [family Scenopinidae], Actorthia frontata Kröber, 1912, Hoplosathe brevistyla Lyneborg & Zaitzev, 1980 [family Therevidae], Hilara sp. [family Empididae], Tomosvaryella demeyeri Kuznetzov, 1993 [family Pipunculidae] and Orchisia costata (Meigen, 1826) [family Muscidae]. In addition, this is the first time to record the four genera Prothaplocnemis Bezzi, Alloxytropus Bezzi, Hilara Meigen and Orchisia Rondani from Saudi Arabia. World and local distributions, diagnoses, feeding behaviors and some colored photographs of recorded species are provided.

Conclusion

In the present study, nine species of predacious and parasitic flies belonging to nine genera and six families are recorded for the first time in Saudi Arabia.
Subthalamic 85 Hz deep brain stimulation improves walking pace and stride length in Parkinson’s disease patients
Authors: Mügge F. , Kleinholdermann U. , Heun A. , Ollenschläger M. , Hannink J. , Pedrosa D. J.
Published: August 2023

Background

Mobile gait sensors represent a compelling tool to objectify the severity of symptoms in patients with idiopathic Parkinson’s disease (iPD), but also to determine the therapeutic benefit of interventions. In particular, parameters of Deep Brain stimulation (DBS) with its short latency could be accurately assessed using sensor data. This study aimed at gaining insight into gait changes due to different DBS parameters in patients with subthalamic nucleus (STN) DBS.

Methods

An analysis of various gait examinations was performed on 23 of the initially enrolled 27 iPD patients with chronic STN DBS. Stimulation settings were previously adjusted for either amplitude, frequency, or pulse width in a randomised order. A linear mixed effects model was used to analyse changes in gait speed, stride length, and maximum sensor lift.

Results

The findings of our study indicate significant improvements in gait speed, stride length, and leg lift measurable with mobile gait sensors under different DBS parameter variations. Notably, we observed positive results at 85 Hz, which proved to be more effective than often applied higher frequencies and that these improvements were traceable across almost all conditions. While pulse widths did produce some improvements in leg lift, they were less well tolerated and had inconsistent effects on some of the gait parameters. Our research suggests that using lower frequencies of DBS may offer a more tolerable and effective approach to enhancing gait in individuals with iPD.

Conclusions

Our results advocate for lower stimulation frequencies for patients who report gait difficulties, especially those who can adapt their DBS settings remotely. They also show that mobile gait sensors could be incorporated into clinical practice in the near future.
Serum S100B is related to insulin resistance and zinc-α2-glycoprotein levels in patients with chronic schizophrenia
Authors: Kalejahi Parinaz , Kheirouri Sorayya , Noorazar Seyed Gholamreza
Published: August 2023

Background

Elevated serum levels of S100B may associate with insulin resistance and other metabolic complication in schizophrenia patients. The aim of this study was to investigate the association of serum S100B levels with cardiometabolic parameters, serum levels of zinc-α2-glycoprotein (ZAG), and the severity of schizophrenia symptoms in schizophrenic patients. We recruited 42 patients with chronic schizophrenia. The participant's body weight (BW), waist circumference (WC), and blood pressure (BP) were measured. Serum levels of low and high-density lipoprotein cholesterol (LDL-c and HDL-C), triglyceride (TG), cholesterol (CHOL), fasting blood glucose (FBG), insulin, S100B, and ZAG levels were determined. The Homeostatic Model Assessment (HOMA) was used to quantify insulin resistance (IR) and the severity of schizophrenia was measured using a positive and negative syndrome scale (PANSS) score.

Results

The results showed that the mean serum S100B levels increased significantly with increasing HOMA-IR and ZAG levels (β = 0.595, 95% confidence interval (CI) (8.722 to 26.002), p < 0.001; and β = 0.334, 95% CI 0.067 to 0.525, p = 0.013 respectively). Patients under treatment with atypical antipsychotic medications (AAPM) had lower serum S100B levels (p = 0.035).

Conclusion

Our results suggest that alteration in glucose metabolism and ZAG secretion may increase serum S100B levels in patients with schizophrenia.
Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma
Authors: Houseni Mohamed , Hady Mahmoud Abdel Aziz Abdel , Abokoura Sameh
Published: August 2023

Objective:

This study’s purpose was to evaluate the response, safety and overall survival of trans-arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with preserved hepatic function.

Methods:

This study was carried out on 25 patients, diagnosed with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT) and underwent hepatic artery infusion chemotherapy (HAIC). Radiological investigations as Triphasic CT or dynamic MRI liver assessment pre and post therapy were acquired. Intra-Arterial chemotherapeutic agent infusion using only doxorubicin was performed.

Results:

Neither of the patients who underwent HAIC developed complete or partial response. Only one patient (4.8%) from 21 patients under HAIC had stable disease. 20 patients (95%) had progressive disease. Progressive disease was in form of progression at the primary tumor site in form of increased focal lesion size, number or vascular invasion. Vascular invasion was seen in one patient (4.8%) in the form of hepatic vein thrombosis. Mean progression free survival was about 2.24 ± 0.88 months. Mean overall survival was about 5.72 ± 0.89 months.

Conclusion:

Our study demonstrated lower clinical efficacy and lower disease control rate of repeated HAIC using doxorubicin only infusion in case of advanced HCC with PVT as compared to combined doxorubicin and cisplatin in previous studies as well as the standard therapy with sorafenib.
Complete perception self-attention network for weak seismic signal recovery in distributed acoustic sensing vertical seismic profile data
Authors: Sui Jilei , Tian Yanan , Li Yue , Wu Ning
Published: August 2023

Distributed acoustic sensing (DAS) is a new technology for acquiring seismic data with high spatial resolution at low cost. Furthermore, in real downhole seismic exploration, DAS can receive some weak signals reflected from deep and thin layers. Unfortunately, some real downhole seismic data received by DAS often are characterized by low quality. Specifically, in real DAS records, desired signals with weak energy often are contaminated by some new noise not presented in seismic data received by conventional electronic geophones. Due to the characteristics of seismic data, such as frequency band aliasing, low signal-to-noise ratio, and complex noise wavefield, existing linear or nonlinear denoising methods based on information processing theories cannot effectively eliminate this complex and multitype noise. Recently, the deep-learning method has been regarded as a powerful tool for background noise attenuation in seismic data. Most of the existing deep-learning methods are concerned with local features and ignore the global features that can be used to enhance their performance further. To simultaneously extract global and local features, we design a novel complete perception self-attention network (CP-SANet) based on the transformer framework and apply it to the denoising of downhole DAS records. The network embeds a transformer module into multilevel encoder-decoder framework. Depth-wise convolution is applied to enhance the local perception capability. Given the transformer’s requirement for a large amount of data, we specifically design abundant seismic data samples using formation models with different parameters. The noise in the data sets is obtained from actual field DAS data. The effectiveness and feasibility of CP-SANet are verified on synthetic and field DAS records. All of the experimental results prove its satisfactory performance compared with some classical and network methods.
Psychiatry in the sultanate of Oman
Authors: Al-Sinawi Hamed , Mirza Hassan
Published: August 2023

Oman has been recognised as the leading country in terms of recent developments in public health. However, there is a shortage of mental health services, which poses challenges for people seeking such services, particularly those from rural areas. This often results in delayed treatment and longer periods of untreated mental illness.
Application of Allostatic Load Theory in Cancer Management and Treatment Outcomes
Authors: Alamoudi Fatmah A. , George Thomas J. , Horgas Ann L. , Huo Zhiguang , Yoon Saunjoo L.
Published: August 2023

Allostatic load is pertinent to explain biopsychological phenomena affecting health outcomes in cancer research
ESR1 Rearrangement as a Diagnostic and Predictive Biomarker in Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Report of Four Cases
Authors: Bini Marta , Gantzer Justine , Dufresne Armelle , Vanacker Hélène , Romeo Clémence , Franceschi Tatiana , Treilleux Isabelle , Pissaloux Daniel , Tirode Franck , Blay Jean-Yves , Ray-Coquard Isabelle , Brahmi Mehdi
Published: August 2023

UTROSCT are a rare entity that can sometimes present as metastatic disease. Hormonal therapy may address this issue.