bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of hospice care on healthcare expenditure among cancer patients
Authors: Jhang Hoyol , Jeong Wonjeong , Zhang Hyun-Soo , Choi Dong-Woo , Kang Hyejung , Park Sohee
Published: August 2023

Purpose

It is necessary to estimate the hospice usage and hospice-related cost for entire cancer patients using nationwide cohort data to establish a suitable ethical and cultural infrastructure. This study aims to show the effects of hospital hospice care on healthcare expenditure among South Korean cancer patients.

Methods

This study is a retrospective cohort study using customized health information data provided by the National Health Insurance Service. Individuals who were diagnosed with stomach, colorectal, or lung cancer between 2003 and 2012 were defined as new cancer patients, which included 7,176 subjects. Patients who died under hospital-based hospice care during the follow-up period from January 2016 to December 2018 comprised the treatment group. Healthcare expenditure was the dependent variable. Generalized estimating equations was used.

Results

Among the subjects, 2,219 (30.9%) had used hospice care at an average total cost of 948,771 (± 3,417,384) won. Individuals who had used hospice care had a lower odds ratio (EXP(β)) of healthcare expenditure than those who did not (Total cost: EXP(β) = 0.27, 95% confidence intervals (CI) = 0.25–0.30; Hospitalization cost: EXP(β) = 0.32, 95% CI = 0.29–0.35; Outpatient cost: EXP(β) = 0.02, 95% CI = 0.02–0.02).

Conclusion

Healthcare expenditure was reduced among those cancer patients in South Korea who used hospice care compared with among those who did not. This emphasizes the importance of using hospice care and encourages those hesitant to use hospice care. The results provide useful insights into both official policy and the existing practices of healthcare systems.
“Handing out non-prescribed antibiotics is storing up trouble for the next generation!” Unpacking multistakeholder views of drivers and potential solutions in Ethiopia
Authors: Belachew Sewunet Admasu , Hall Lisa , Selvey Linda A
Published: August 2023

Background

Antibiotic resistance is a global health crisis, with inappropriate antibiotic use often being linked to non-prescribed antibiotic dispensing practices. This study aimed to examine the perspectives of multiple stakeholders on the drivers and potential solutions for non-prescribed antibiotic dispensing in Ethiopian community drug retail outlets (CDROs). Despite the prescription only use policies, the practice remains prevalent in Ethiopia. Many factors are thought to contribute to this issue, although little research is available for non-urban settings.

Methods

A phenomenological qualitative study was conducted. Pharmacy professionals (owners or employees) working in non-urban towns CDROs were selected through a simulated client study, which identified CDROs that had dispensed antibiotics without a prescription. Some high-level decision makers in the Ethiopian health system were also purposively selected. Interviews were conducted in-person and over the phone or via Zoom. The interview data were transcribed verbatim, translated to English, and thematically analysed. NVivo 12 software was used to assist with coding.

Results

CDRO pharmacy professionals (n = 18) and five decision makers were interviewed. Most professionals (61%) were pharmacists working in drug stores, with one to 11 years of work experience. Several contributing factors were identified at the level of patients, CDRO staff, and the healthcare system. These included economic interests, inadequate knowledge and inappropriate attitudes about antibiotic use or supply, and issues within the healthcare system included inaccessibility and insufficient capacity, absence of or a weak enforcement of prescription-only regulations or service supervision. Additionally, patient-related factors included a lack of knowledge and inappropriate attitudes about antibiotics use and their supply, previous successful treatment experience and a culture of seeking out antibiotics.

Conclusions

A complex set of modifiable factors related to patients, CDRO staff and healthcare system were identified that contribute to the non-prescribed supply of antibiotics. Due to this complexity, a single solution will not resolve the issues. Therefore, a range of multifaceted solutions have been suggested, including stricter regulation, increasing availability and accessibility of healthcare services, collaboration, and local consensus-building among CDROs, regular training for CDRO staff, and using community social events to educate the public about responsible use of antibiotics.
Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration
Authors: Kunze Reiner , Fischer Silvia , Marti Hugo H. , Preissner Klaus T.
Published: August 2023

Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered by danger associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue. Besides protein-related DAMPs or “alarmins”, numerous nucleic acid DAMPs exist in body fluids, such as cell-free nuclear and mitochondrial DNA as well as different species of extracellular RNA, collectively termed as self-extracellular nucleic acids (SENAs). Among these, microRNA, long non-coding RNAs, circular RNAs and extracellular ribosomal RNA constitute the majority of RNA-based DAMPs. Upon tissue injury, necrosis or apoptosis, such SENAs are released from neuronal, immune and other cells predominantly in association with extracellular vesicles and may be translocated to target cells where they can induce intracellular regulatory pathways in gene transcription and translation. The majority of SENA-induced signaling reactions in the brain appear to be related to neuroinflammatory processes, often causally associated with the onset or progression of the respective disease. In this review, the impact of the diverse types of SENAs on neuroinflammatory and neurodegenerative diseases will be discussed. Based on the accumulating knowledge in this field, several specific antagonistic approaches are presented that could serve as therapeutic interventions to lower the pathological outcome of the indicated brain disorders.
Performance and feasibility of reactive surveillance and response strategies for malaria elimination in Vietnam: a mixed-methods study
Authors: Win Han Oo  , Nguyen Xuan Thang , Ngo Thi Van Anh , Ngo Duc Thang , Win Htike  , Aye Tun Nilar , Kaung Myat Thu  , Cutts Julia , Nguyen T Hong Phuc , May Chan Oo  , Ei Phyu Htwe  , Aung Khine Zaw  , O’Flaherty Katherine , Agius Paul A. , Fowkes Freya J. I.
Published: August 2023

Background

To enhance malaria elimination, Vietnam adopted a Reactive Surveillance and Response (RASR) Strategy in which malaria case notification and investigation must be completed within 2 days followed by a focus investigation within 7 days. The nationwide performance of Vietnam’s RASR strategy has yet to be evaluated. This study aims to evaluate the performance and feasibility of RASR in Vietnam, thereby providing recommendations for improved RASR.

Methods

To assess malaria RASR in Vietnam, a mixed-methods study of (1) secondary data analysis of nationwide malaria case-based dataset from 2017 to 2021; (2) a quantitative survey, and (3) qualitative in-depth interviews and focus group discussions administered to central, provincial and district level stakeholders/staff and to the commune and community level front line health services providers was conducted.

Results

In Vietnam, there are guidelines and procedures for implementation of each step of RASR. The completeness of case notification on the reported monthly aggregated data was very high in both the paper-based (12,463/12,498, 99.7% in 2017–2020) and electronic reporting systems (467/467, 100% in 2021 when electronic reporting was introduced); however, there were delays in notification while using the paper-based system (timely notification—7,978/12,498, 63.8%). In 2021, the completeness (453/467, 97.0%) and timeliness (371/467, 79.4%) of case investigation were found to be high. Reactive case detection was the major focus investigation response, with fever screening achievement of 88.6% (11,481 / 12,965) and 88.5% (11,471 / 12,965) among index case and neighbouring household members, respectively.

Conclusions

Overall, there was policy commitment for implementation of RASR in Vietnam. The completeness and timeliness of case notification and case investigation were high and improved after the introduction of the electronic reporting system. More evidence is required for reactive case detection in defining the screening area or population.
Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study
Authors: Saifon Woraseth , Karaketklang Khemajira , Jitmuang Anupop
Published: August 2023

Background

Central nervous system tuberculosis (CNS TB) is a severeMycobacterium tuberculosis(MTB) infection. It is unclear whether a patient’s immune status alters the clinical manifestations and treatment outcomes of CNS TB.

Methods

Between January 2007–December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID).

Results

Of 310 subjects, 160 (51.6%) were in the ID group—132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status —HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups.

Conclusions

TBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients.
Expression of genes regulating cell division in porcine follicular granulosa cells
Authors: Kulus Jakub , Kranc Wiesława , Kulus Magdalena , Dzięgiel Piotr , Bukowska Dorota , Mozdziak Paul , Kempisty Bartosz , Antosik Paweł
Published: August 2023

Background

Cell cycle regulation influences the proliferation of granulosa cells and affects many processes related to ovarian folliclular growth and ovulation. Abnormal regulation of the cell cycle can lead to many diseases within the ovary. The aim of this study was to describe the expression profile of genes within granulosa cells, which are related to the formation of the cytoskeleton, organization of cell organelles inside the cell, and regulation of cell division. Established in vitro primary cultures from porcine ovarian follicle granulosa cells were maintained for 48, 96, 144 h and evaluated via microarray expression analysis.

Results

Analyzed genes were assigned to 12 gene ontology groups "actin cytoskeleton organization", "actin filament organization", "actin filament—based process", "cell—matrix adhesion", "cell—substrate adhesion", "chromosome segregation", "chromosome separation", "cytoskeleton organization", "DNA integrity checkpoint", "DNA replication initiation", "organelle fision", "organelle organization". Among the genes with significantly changed expression, those whose role in processes within the ovary are selected for consideration. Genes with increased expression include (ITGA11, CNN1, CCl2, TPM2, ACTN1, VCAM-1, COL3A1, GSN, FRMD6, PLK2). Genes with reduced expression inlcude (KIF14, TACC3, ESPL1, CDC45, TTK, CDC20, CDK1, FBXO5, NEK2—NIMA, CCNE2). For the results obtained by microarray expressions, quantitative validation by RT-qPCR was performed.

Conclusions

The results indicated expression profile of genes, which can be considered as new molecular markers of cellular processes involved in signaling, cell structure organization. The expression profile of selected genes brings new insight into regulation of physiological processes in porcine follicular granulosa cells during primary in vitro culture.
Fixators dynamization for delayed union and non-union of femur and tibial fractures: a review of techniques, timing and influence factors
Authors: Hu Minhua , Zeng Wenxing , Zhang Jingtao , Feng Yuanlan , Ma Luyao , Huang Feng , Cai Qunbin
Published: August 2023

The optimal balance between mechanical environment and biological factors is crucial for successful bone healing, as they synergistically affect bone development. Any imbalance between these factors can lead to impaired bone healing, resulting in delayed union or non-union. To address this bone healing disorder, clinicians have adopted a technique known as "dynamization" which involves modifying the stiffness properties of the fixator. This technique facilitates the establishment of a favorable mechanical and biological environment by changing a rigid fixator to a more flexible one that promotes bone healing. However, the dynamization of fixators is selective for certain types of non-union and can result in complications or failure to heal if applied to inappropriate non-unions. This review aims to summarize the indications for dynamization, as well as introduce a novel dynamic locking plate and various techniques for dynamization of fixators (intramedullary nails, steel plates, external fixators) in femur and tibial fractures. Additionally, Factors associated with the effectiveness of dynamization are explored in response to the variation in dynamization success rates seen in clinical studies.
Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts
Authors: Boso Daniele , Tognon Martina , Curtarello Matteo , Minuzzo Sonia , Piga Ilaria , Brillo Valentina , Lazzarini Elisabetta , Carlet Jessica , Marra Ludovica , Trento Chiara , Rasola Andrea , Masgras Ionica , Caporali Leonardo , Del Ben Fabio , Brisotto Giulia , Turetta Matteo , Pastorelli Roberta , Brunelli Laura , Navaglia Filippo , Esposito Giovanni , Grassi Angela , Indraccolo Stefano
Published: August 2023

Background

Genetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis.

Methods

Clonal populations, obtained from both ovarian cancer cell lines (IGROV-1 and SKOV3) and tumor xenografts upon glucose deprivation, were defined as glucose deprivation resistant (GDR) or glucose deprivation sensitive (GDS) clones based on their in vitro behaviour. GDR and GDS clones were characterized using a multi-omics approach, including genetic, transcriptomic and metabolic analysis, and tested for their tumorigenic potential and reaction to anti-angiogenic therapy.

Results

Two clonal populations, GDR and GDS, with strikingly different viability following in vitro glucose starvation, were identified in ovarian cancer cell lines. GDR clones survived and overcame glucose starvation-induced stress by enhancing mitochondrial oxidative phosphorylation (OXPHOS) and both pyruvate and lipids uptake, whereas GDS clones were less able to adapt and died. Treatment of ovarian cancer xenografts with the anti-VEGF drug bevacizumab positively selected for GDR clones that disclosed increased tumorigenic properties in NOD/SCID mice. Remarkably, GDR clones were more sensitive than GDS clones to the mitochondrial respiratory chain complex I inhibitor metformin, thus suggesting a potential therapeutic strategy to target the OXPHOS-metabolic dependency of this subpopulation.

Conclusion

A glucose-deprivation resistant population of ovarian cancer cells showing druggable OXPHOS-dependent metabolic traits is enriched in experimental tumors treated by anti-VEGF therapy.
Cross-protein transfer learning substantially improves disease variant prediction
Authors: Jagota Milind , Ye Chengzhong , Albors Carlos , Rastogi Ruchir , Koehl Antoine , Ioannidis Nilah , Song Yun S.
Published: August 2023

Background

Genetic variation in the human genome is a major determinant of individual disease risk, but the vast majority of missense variants have unknown etiological effects. Here, we present a robust learning framework for leveraging saturation mutagenesis experiments to construct accurate computational predictors of proteome-wide missense variant pathogenicity.

Results

We train cross-protein transfer (CPT) models using deep mutational scanning (DMS) data from only five proteins and achieve state-of-the-art performance on clinical variant interpretation for unseen proteins across the human proteome. We also improve predictive accuracy on DMS data from held-out proteins. High sensitivity is crucial for clinical applications and our model CPT-1 particularly excels in this regime. For instance, at 95% sensitivity of detecting human disease variants annotated in ClinVar, CPT-1 improves specificity to 68%, from 27% for ESM-1v and 55% for EVE. Furthermore, for genes not used to train REVEL, a supervised method widely used by clinicians, we show that CPT-1 compares favorably with REVEL. Our framework combines predictive features derived from general protein sequence models, vertebrate sequence alignments, and AlphaFold structures, and it is adaptable to the future inclusion of other sources of information. We find that vertebrate alignments, albeit rather shallow with only 100 genomes, provide a strong signal for variant pathogenicity prediction that is complementary to recent deep learning-based models trained on massive amounts of protein sequence data. We release predictions for all possible missense variants in 90% of human genes.

Conclusions

Our results demonstrate the utility of mutational scanning data for learning properties of variants that transfer to unseen proteins.
Duroplasty for injured cervical spinal cord with uncontrolled swelling: protocol of the DISCUS randomized controlled trial
Authors: Saadoun Samira , Grassner Lukas , Belci Maurizio , Cook Jonathan , Knight Ruth , Davies Lucy , Asif Hasan , Visagan Ravindran , Gallagher Mathew J. , Thomé Claudius , Hutchinson Peter J. , Zoumprouli Argyro , Wade Julia , Farrar Nicola , Papadopoulos Marios C.
Published: August 2023

Background

Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone.

Methods

This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results).

Discussion

We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care.

Trial registration

IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021).
Efficacy of five-step shoulder manipulation for rotator cuff-related shoulder pain: protocol for a multicenter randomized controlled trial
Authors: Liu Shuang , Liu Jin-Tao , Chen Lin , Fan Tian-You , Cui Xue-Jun , Cheng Shao-Dan , Chen Yan-Jiao , Shi Qi , Xue Chun-Chun , Li Xiao-Feng
Published: August 2023

Background

Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder disorders. In China, manipulation has been used extensively for the treatment of patients with RCRSP. However, high-quality clinical evidence to support the therapeutic effect of manipulation is still limited.

Methods

A multicenter, participant-, outcome assessor-, and data analyst-blinded, randomized, placebo-controlled trial will be conducted. A total of 280 participants with RCRSP will be recruited from three hospitals and randomly assigned to a five-step shoulder manipulation (FSM) group or a sham manipulation (SM) group. Each group will receive four weekly treatment sessions, with all participants performing exercises at home for 12 weeks. Assessments, namely the Constant–Murley score, visual analog scale, range of motion, and 36-Item Short Form Survey, will be made at baseline, 4, 12, 18, and 24 weeks. Adverse events during the study will also be recorded.

Discussion

This is a pragmatic clinical trial to evaluate the efficacy and safety of FSM in patients with RCRSP. The findings of this study will provide worthy clinical evidence for manual therapy for RCRSP.

Trial registration

China Registered Clinical Trial Registration Center ChiCTR2000037577. Registered on 29 August 2020.
Proximal ROw carpectOmy versus four-corner Fusion (PROOF-trial) for osteoarthritis of the wrist: study protocol for multi-institutional double-blinded randomized controlled trial
Authors: Alanen Mikko , Stjernberg-Salmela Susanna , Waris Eero , Karjalainen Teemu , Miettunen Jouko , Ryhänen Jorma , Aspinen Samuli
Published: August 2023

Background

Scapholunate advanced collapse (SLAC) and scaphoid non-union advanced collapse (SNAC) are common types of wrist osteoarthritis (OA). Non-operative treatment consists of pain medication, splinting, and avoiding activities that induce pain. However, in case a course of conservative treatment is unsuccessful, operative treatment is needed. The two most conventional operative approaches for SLAC/SNAC OA are four-corner arthrodesis (FCA) and proximal row carpectomy (PRC). Although FCA is the gold-standard operative technique and may lead to superior grip strength, the evident benefit of PRC is that it obviates any need for hardware removal and controlling for bony union. To date, no high-quality randomized controlled trial comparing FCA and PRC exists. As clinical outcomes seem comparable, a trial that assesses patient-reported outcomes, adverse events, and secondary operations may guide clinical decision making between these two procedures. Thus, the aim of this multi-institutional double-blind randomized controlled trial is to study whether PRC is non-inferior to FCA in treating SLAC/SNAC OA. We hypothesize that PRC is non-inferior to FCA with lower economic expanses.

Methods

The trial is designed as a randomized, controlled, patient- and outcome-assessor blinded multicenter, two-armed 1:1 non-inferiority trial. Patients with SLAC/SNAC-induced wrist pain meeting trial inclusion criteria will undergo wrist arthroscopy to further assess eligibility. Each patient eligible for the trial will be randomly assigned to undergo either FCA or PRC. The primary endpoint of this study is the Patient Rated Wrist Evaluation (PRWE) at 1-year after FCA versus PRC. Secondary outcomes include Quick-Disabilities of the Arm, Shoulder and Hand, EQ-5D-5L, pain, grip strength, wrist active range of motion, radiographic evaluation, and adverse events. Trial design, methods, and statistical analysis plan will be presented here.

Discussion

We present an RCT design comparing FCA vs PRC for SLAC/SNAC-induced OA. The results of this trial will assist in decision making when planning surgery for SLAC/SNAC.

Trial registration

ClinicalTrials.gov NCT04260165. Registered February 7, 2020.
Transcriptional variation in Babesia gibsoni (Wuhan isolate) between in vivo and in vitro cultures in blood stage
Authors: Han Zhen , Zheng Yaxin , Shi Yu , Chen Fangwei , Wu Chenglong , Wang Lingna , Lu Shiyu , Li Dongfang , Guan Xingai , He Lan , Zhao Junlong
Published: August 2023

Background

Babesia gibsoni, the causative agent of canine babesiosis, belongs to the phylum Apicomplexa. The development of in vitro culture technology has driven research progress in various kinds of omics studies, including transcriptomic analysis of Plasmodium spp. between in vitro and in vivo environments, which has prompted the observation of diagnostic antigens and vaccine development. Nevertheless, no information on Babesia spp. could be obtained in this respect, which greatly hinders the further understanding of parasite growth and development in the blood stage.

Methods

In this study, considerable changes in the morphology and infectivity of continuous in vitro cultured B. gibsoni (Wuhan isolate) were observed compared to in vivo parasites. Based on these changes, B. gibsoni (Wuhan isolate) was collected from both in vivo and in vitro cultures, followed by total RNA extraction and Illumina transcriptome sequencing. The acquired differentially expressed genes (DEGs) were validated using qRT-PCR, and then functionally annotated through several databases. The gene with the greatest upregulation after in vitro culture was cloned from the genome of B. gibsoni (Wuhan isolate) and characterized by western blotting and indirect immunofluorescence assay for detecting the native form and cellular localization.

Results

Through laboratory cultivation, multiple forms of parasites were observed, and the infectivity of in vitro cultured parasites in dogs was found to be lower. Based on these changes, Illumina transcriptome sequencing was conducted, showing that 377 unigenes were upregulated and 334 unigenes were downregulated. Notably, an AP2 transcription factor family, essential for all developmental stages of parasites, was screened, and the transcriptional changes in these family members were tested. Thus, the novel AP2 transcription factor gene (BgAP2-M) with the highest upregulated expression after in vitro adaptation was selected. This gene comprises an open reading frame (ORF) of 1989 base pairs encoding a full-length protein of 662 amino acids. BgAP2-M contains one AP2 domain and one ACDC conserved domain, which may be involved in the nuclear biology of parasites. The prepared polyclonal antibodies against the BgAP2-M peptides further detected a native size of ~ 73 kDa and were localized to the nuclei of B. gibsoni.

Conclusion

This study presents a thorough transcriptome analysis of B. gibsoni in vivo and in vitro for the first time, contributing to a detailed understanding of the effects of environmental changes on the growth and development of parasites in the blood stage. Moreover, it also provides a deeper investigation for the different members of the ApiAP2 transcription factor family as various life stage regulators in Babesia spp.

Graphical Abstract
The potential for zoonotic malaria transmission in five areas of Indonesia inhabited by non-human primates
Authors: Permana Dendi Hadi , Hasmiwati  , Suryandari Dwi Anita , Rozi Ismail Ekoprayitno , Syahrani Lepa , Setiadi Wuryantari , Irawati Nuzulia , Rizaldi  , Wangsamuda Suradi , Yusuf Yenni , Irdayanti  , Aswad Hijral , Asih Puji Budi Setia , Syafruddin Din
Published: August 2023

Background

Indonesia is home to many species of non-human primates (NHPs). Deforestation, which is still ongoing in Indonesia, has substantially reduced the habitat of NHPs in the republic. This has led to an intensification of interactions between NHPs and humans, which opens up the possibility of pathogen spillover. The aim of the present study was to determine the prevalence of malarial parasite infections in NHPs in five provinces of Indonesia in 2022. Species of the genus Anopheles that can potentially transmit malarial pathogens to humans were also investigated.

Methods

An epidemiological survey was conducted by capturing NHPs in traps installed in several localities in the five provinces, including in the surroundings of a wildlife sanctuary. Blood samples were drawn aseptically after the NHPs had been anesthetized; the animals were released after examination. Blood smears were prepared on glass slides, and dried blood spot tests on filter paper. Infections with Plasmodium spp. were determined morphologically from the blood smears, which were stained with Giemsa solution, and molecularly through polymerase chain reaction and DNA sequencing using rplU oligonucleotides. The NHPs were identified to species level by using the mitochondrial cytochrome c oxidase subunit I gene and the internal transcribed spacer 2 gene as barcoding DNA markers. Mosquito surveillance included the collection of larvae from breeding sites and that of adults through the human landing catch (HLC) method together with light traps.

Results

Analysis of the DNA extracted from the dried blood spot tests of the 110 captured NHPs revealed that 50% were positive for Plasmodium, namely Plasmodium cynomolgi, Plasmodium coatneyi, Plasmodium inui, Plasmodium knowlesi and Plasmodium sp. Prevalence determined by microscopic examination of the blood smears was 42%. Species of the primate genus Macaca and family Hylobatidae were identified by molecular analysis. The most common mosquito breeding sites were ditches, puddles and natural ponds. Some of the Anopheles letifer captured through HLC carried sporozoites of malaria parasites that can cause the disease in primates.

Conclusions

The prevalence of malaria in the NHPs was high. Anopheles letifer, a potential vector of zoonotic malaria, was identified following its collection in Central Kalimantan by the HLC method. In sum, the potential for the transmission of zoonotic malaria in several regions of Indonesia is immense.

Graphical Abstract
Effectiveness of home-based exercise in breast cancer survivors: a randomized clinical trial
Authors: Farajivafa Vahid , Khosravi Nasim , Rezaee Nilofar , Koosha Maryam , Haghighat Shahpar
Published: August 2023

Background

Breast cancer patients are recommended to engage in regular exercise. In developing countries, where there is a lack of facilities to offer specialized, supervised exercise for this population, regularly exercising might be a challenge. We aimed to evaluate the effectiveness of a home-based intervention in this population.

Methods

Breast cancer survivors were randomly assigned to either the home-based exercise program or the usual care group. Exercise intervention included walking, balance, and stretch exercises, along with weekly follow-up telephone calls. Quality of life (QOL) was evaluated using EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and the predicted VO2 peak was measured using the Ebbeling submaximal treadmill test.

Results

Eighty-nine patients were enrolled in the study. Reported minutes of exercise gradually increased from 40.7 min per week in week 1 to 116.9 min per week in week 12. This intervention improved global QOL (P = 0.001), social functioning (P = 0.04), and the predicted VO2 peak (P = 0.01).

Conclusion

This home-based exercise regime effectively increased quality of life and physical activity levels.

Trial registry

Iranian Registry of Clinical Trials identifier: IRCT20140810018746N1, prospectively registered 08/01/2018, https://en.irct.ir/trial/27959.
NSP4 as adjuvant for immunogenicity and design of effective therapeutic HPV16 E6/E7/L1 DNA vaccine in tumor-bearing and healthy C57BL/6 mice
Authors: Sadr-Momtaz Sahar , Aftabi Maryam , Behboudi Emad , Naderi Malihe , Hashemzadeh-Omran Anahita , Moradi Abdolvahab
Published: August 2023

Introduction

In humans, approximately 5% of all cancers are attributable to HPV infection. Prophylactic vaccines can inhibit viral migration and persistence. However, further studies are still required to develop such treatments. To achieve this goal, we designed a therapeutic HPV DNA vaccine encoding a construct of E6/E7/L1 and used NSP4 antigen as an adjuvant to assess the efficiency of this construct in generating antigen-specific antitumor immune responses.

Materials and methods

Sixty female C57BL/6 mice (6–8 weeks old) were purchased from the Institute Pasteur of Iran. Through a subcutaneous (s.c) injection of a suspension of 100 µl PBS containing 106 TC-1 cells/mouse in the back side, 30 of them became cancerous, while 30 of them were healthy control mice. To amplify E6/E7/L1-pcDNA3 and NSP4-pcDNA3, the competent cells of DH5α and to generate a tumor, TC-1 cell line was used. Mice were then immunized with the HPV DNA vaccine. Cell proliferation was assessed by MTT assay. Finally, cytokine responses (IL-4, IL-12, IFN- γ) were measured in the supernatant of mice spleen cells.

Result

Mice receiving the NSP4/E6-E7-L1 vaccine had the highest stimulatory index compared to other groups, although it was not statistically significant. Interleukin 4/12 and IFN-γ production were significantly higher in E6-E7-L1 / NSP4 group and E6-E7-L1 group compared to other groups (P < 0.05). Among different groups, E6/E7/L1 + NSP4 group was able to slow down the tumor growth process, but it was not significant (p > 0.05). Among the aforementioned cytokines, IFN-γ and IL-12 are among the cytokines that stimulate the Th1 pathway and IL-4 cytokine stimulates the Th2 pathway and B lymphocytes.

Conclusion

Our data revealed that the present vaccine can reduce tumor size, and cytokine measurement showed that it stimulates innate and acquired immune responses, thus it can be a therapeutic vaccine in the tumor-bearing mice model.
Myelin oligodendrocyte glycoprotein antibody-associated disease as a novel presentation of central nervous system autoimmunity in a pediatric patient with Wiskott-Aldrich syndrome
Authors: Xie Vivien X. , File Wilson , Wiedl Christina , Ward Brant R. , Saldaña Blachy Dávila , Keller Michael D. , Kornbluh Alexandra B.
Published: August 2023

Background

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene that leads to increased susceptibility to infections, thrombocytopenia, eczema, malignancies, and autoimmunity. Central nervous system (CNS) autoimmune manifestations are uncommon.

Case Presentation

We describe the case of a five-year-old boy with refractory thrombocytopenia and iron deficiency anemia who developed relapsing bilateral optic neuritis. Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) via serum fluorescence-activated cell sorting assay was positive (titer 1:100), confirming a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). At age six, molecular panel testing for genes associated with primary immunodeficiency identified a missense WAS gene variant. He was subsequently found to have decreased WAS protein expression, consistent with a diagnosis of WAS.

Conclusions

This case expands the reported spectrum of CNS autoimmunity associated with WAS and may help to inform long-term therapeutic options.
Trivalvular nonbacterial thrombotic endocarditis in a patient with colon adenocarcinoma: a case report
Authors: Bagheri Abdolhamid , Khani Mohammad , Akbari Tooba , Ghadirzadeh Erfan , Charkazi Elham , Ghorbani Parastoo
Published: August 2023

Background

Nonbacterial thrombotic endocarditis is a rare complication of prothrombotic states such as neoplasms that can cause valvular dysfunction and life-threatening complications. Nonbacterial thrombotic endocarditis usually affects the left-sided valves; however, only a minority of cases involving the tricuspid valve have been reported in medical literature.

Case presentation

The current report describes trivalvular involvement by nonbacterial thrombotic endocarditis in a 54-year-old Azeri female patient with metastatic colorectal carcinoma. This case underlines the necessity of evaluating nonbacterial thrombotic endocarditis as a possible consequence in cancer patients. When thromboembolic events are found in the presence of a hypercoagulable state (such as malignancy) and no growth on blood cultures, nonbacterial thrombotic endocarditis could be suspected as the cause.

Conclusion

It is critical to achieve early diagnosis in such a setting to initiate treatment plans and prevent further complications rapidly.
DeepSAT: Learning Molecular Structures from Nuclear Magnetic Resonance Data
Authors: Kim Hyun Woo , Zhang Chen , Reher Raphael , Wang Mingxun , Alexander Kelsey L. , Nothias Louis-Félix , Han Yoo Kyong , Shin Hyeji , Lee Ki Yong , Lee Kyu Hyeong , Kim Myeong Ji , Dorrestein Pieter C. , Gerwick William H. , Cottrell Garrison W.
Published: August 2023

The identification of molecular structure is essential for understanding chemical diversity and for developing drug leads from small molecules. Nevertheless, the structure elucidation of small molecules by Nuclear Magnetic Resonance (NMR) experiments is often a long and non-trivial process that relies on years of training. To achieve this process efficiently, several spectral databases have been established to retrieve reference NMR spectra. However, the number of reference NMR spectra available is limited and has mostly facilitated annotation of commercially available derivatives. Here, we introduce DeepSAT, a neural network-based structure annotation and scaffold prediction system that directly extracts the chemical features associated with molecular structures from their NMR spectra. Using only the 1H-13C HSQC spectrum, DeepSAT identifies related known compounds and thus efficiently assists in the identification of molecular structures. DeepSAT is expected to accelerate chemical and biomedical research by accelerating the identification of molecular structures.
Linking sustainability and the Fourth Industrial Revolution: a monitoring framework accounting for technological development
Authors: Siekmann Florian , Schlör Holger , Venghaus Sandra
Published: August 2023

Background

In this article, the concept of the Fourth Industrial Revolution and related implications for the measurement of sustainable development are analyzed. Technological innovations can play an important role in countering errant developments of the past and can support the transformation process towards a green economy in pursuit of the Sustainable Development Goals. On the other hand, they pose challenges to the social control of technology and represent a methodical quandary known as the Collingridge dilemma. The core statement of the dilemma is that the implications of new technologies will only be fully visible once they are embedded in socio-economic-ecological systems when the possibilities to control diminish. The main objective of this study is thus to develop a monitoring framework enabling the ex ante assessment of related technological shifts and their implications for sustainable development.

Results

To approach the resulting difficulties for sustainability monitoring, digitization indicators should be accounted for in the German Sustainable Development Strategy. An enhanced strategy complemented by related Global Competitiveness Index 4.0 indicators, for which the Word Economic Forum assumes a modest link between competitiveness and inequality, illustrates the feasibility of linking research regarding the Fourth Industrial Revolution and sustainable development to measure its social and environmental consequences. The newly developed Sustainable Digital Socio-Economic-Ecological Indicator System categorizes the sustainability indicators into one index covering all Sustainable Development Goals along with four sub-indices emphasizing crucial aspects relevant to navigating a successful transformation. This novel and innovative approach is illustrated using the examples of Germany.

Conclusions

The Fourth Industrial Revolution is fundamentally driven by introducing renewable energy resources as a new energy regime. However, the effects extend beyond energy and necessitate comprehensive measurement frameworks for assessing sustainable development implications. This work contributes by analyzing the related impact on sustainable development and providing decision-makers with new insights for early recognition. Preliminary results for Germany expose a discrepancy between the status quo and the desired pathway, indicating emerging effects of the Fourth Industrial Revolution on inequality, employment, and education. While none of the sectors are sustainable, the sub-index analysis highlights distinct disparities among economic, social, and ecological sectors.
Pulmonary endarterectomy in patients with occlusive isolated pulmonary vasculitis
Authors: Ma Jiexu , Song Wu , Xu Hang , Zhong ZhaoJi , Huyan Yige , Liu Sheng
Published: August 2023

Background

Isolated pulmonary vasculitis (IPV) is a rare, insidious, and localized inflammatory disease affecting the pulmonary arteries, often leading to severe luminal obstruction. The prognosis for patients with occlusive IPV is poor, and there is currently a lack of effective treatments. The objective of this study was to evaluate the performance of pulmonary endarterectomy (PEA) as a treatment for occlusive IPV.

Methods

This single-center retrospective analysis included patients who received PEA for occlusive IPV between January 2018 and June 2022. Clinical characteristics and hemodynamic parameters were evaluated at baseline and follow-up.

Results

Among 114 consecutive patients who underwent PEA, occlusive IPV was identified in 7 patients. Two patients underwent bilateral PEA for the involvement of both pulmonary arteries. Patch angioplasty was performed to treat four severe constrictions. One patient died from residual pulmonary hypertension after limited PEA of a transmural vascular lesion. In addition, no obvious surgical complications were observed. Three months after PEA, a substantial relief in symptoms was achieved. Also, there is a decrease in the mean pulmonary artery pressure (median 33 [20–48] mmHg before versus median 21 [16–26] mmHg after; P < 0.018) and pulmonary arterial resistance (median 234 [131–843] dyn.s.cm−5 versus median 180 [150–372] dyn.s.cm−5; P = 0.310). Three patients experienced a relapse of restenosis of the treated arteries within a 6-month follow-up period, despite daily oral prednisolone administration. They were treated with balloon pulmonary angioplasty of both the main pulmonary arteries and branches.

Conclusions

PEA is a valuable choice for treating occlusive IPV, with notable hemodynamic and clinical advantages. To increase long-term vascular patency, complete management should be optimized.
A review of the application of mesenchymal stem cells in the field of hematopoietic stem cell transplantation
Authors: Lin Ting , Yang Yunfan , Chen Xinchuan
Published: August 2023

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for many malignant hematological diseases. Mesenchymal stem cells (MSCs) are nonhematopoietic stem cells with strong self-renewal ability and multidirectional differentiation potential. They have the characteristics of hematopoietic support, immune regulation, tissue repair and regeneration, and homing. Recent studies have shown that HSCT combined with MSC infusion can promote the implantation of hematopoietic stem cells and enhance the reconstruction of hematopoietic function. Researchers have also found that MSCs have good preventive and therapeutic effects on acute and chronic graft-versus-host disease (GVHD), but there is still a lack of validation in large-sample randomized controlled trials. When using MSCs clinically, it is necessary to consider their dose, source, application time, application frequency and other relevant factors, but the specific impact of the above factors on the efficacy of MSCs still needs further clinical trial research. This review introduces the clinical roles of MSCs and summarizes the most recent progress concerning the use of MSCs in the field of HSCT, providing references for the later application of the combination of MSCs and HSCT in hematological diseases.
Prepulse inhibition deficit as a transdiagnostic process in neuropsychiatric disorders: a systematic review
Authors: Santos-Carrasco Daniel , De la Casa Luis Gonzalo
Published: August 2023

Background

Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple pathologies. A phenomenon disrupted in several disorders is prepulse inhibition (PPI) of the startle response, in which startle to an intense sensory stimulus, or pulse, is reduced if a weak stimulus, or prepulse, is previously presented.

Objective and methods

The present systematic review analyzed the role of PPI deficit as a possible transdiagnostic process for four main groups of neuropsychiatric disorders: (1) trauma-, stress-, and anxiety-related disorders (2) mood-related disorders, (3) neurocognitive disorders, and (4) other disorders such as obsessive-compulsive, tic-related, and substance use disorders. We used Web of Science, PubMed and PsycInfo databases to search for experimental case-control articles that were analyzed both qualitatively and based on their potential risk of bias. A total of 64 studies were included in this systematic review. Protocol was submitted prospectively to PROSPERO 04/30/2022 (CRD42022322031).

Results and conclusion

The results showed a general PPI deficit in the diagnostic groups mentioned, with associated deficits in the dopaminergic neurotransmission system, several areas implied such as the medial prefrontal cortex or the amygdala, and related variables such as cognitive deficits and anxiety symptoms. It can be concluded that the PPI deficit appears across most of the neuropsychiatric disorders examined, and it could be considered as a relevant measure in translational research for the early detection of such disorders.